bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic structure measurements of dense plasmas
Authors: Gregori G. , Glenzer S. H. , Rogers F. J. , Pollaine S. M. , Landen O. L. , Blancard C. , Faussurier G. , Renaudin P. , Kuhlbrodt S. , Redmer R.
Published: April 2004

This paper presents an improved analytical expression for the x-ray dynamic structure factor from a dense plasma which includes the effects of weakly bound electrons. This result can be applied to describe scattering from low to moderate Z plasmas, and it covers the entire range of plasma conditions that can be found in inertial confinement fusion experiments, from ideal to degenerate up to moderately coupled systems. The theory is used to interpret x-ray scattering experiments from solid density carbon plasmas and to extract accurate measurements of electron temperature, electron density, and charge state. The experimental results are applied to validate various equation-of-state models for carbon plasmas.
Detection of trinitrotoluene via deflagration on a microcantilever
Authors: Pinnaduwage L. A. , Wig A. , Hedden D. L. , Gehl A. , Yi D. , Thundat T. , Lareau R. T.
Published: April 2004

We describe in detail the detection of deflagration of trinitrotoluene (TNT) deposited on a piezoresistive microcantilever and point out its possible use for explosive-vapor detection. The deflagration of TNT causes the cantilever to bend (due to released heat) and its resonance frequency to shift (due to mass unloading). Explosive vapors provide unique responses that are absent for “interferences” such as water or alcohol vapors. The proposed sensor makes possible a sensitive, miniature explosives detection device that may be deployed in large numbers. The minimum amount of TNT detected on the cantilever depends on the cantilever dimensions and was ≈50 pg for the batch of cantilevers used.
Photoacoustic study of explosive boiling of a 2-propanol layer of variable thickness on a KrF excimer laser-heated Si substrate
Authors: Kudryashov Sergey I. , Allen Susan D.
Published: April 2004

The dynamics of explosive boiling of a 2-propanol layer of variable thickness on a Si substrate heated by a nanosecond KrF excimer laser was studied using a contact photoacoustic technique. The transition from acoustic generation at a free Si boundary to that at a rigid alcohol/Si boundary accompanied by a sharp increase of acoustic generation efficiency was found above a laser fluence threshold of 0.17 J/cm2 and a liquid layer thickness greater than 0.25 μm due to subnanosecond near-critical explosive boiling of the superheated liquid layer near the hot absorbing Si substrate. The gradual increase of the photoacoustic response of the superheated alcohol with increasing thickness of the liquid film at fluences above the explosive boiling threshold was attributed to a diffraction effect due to the fluence- and time-dependent increase of the area undergoing explosive boiling. A model describing photoacoustic generation and subsequent lift-off of the entire liquid layer in this experimental “thin transparent liquid layer/solid absorbing substrate” geometry under near-critical explosive boiling conditions has been proposed.
Ambipolar organic field-effect transistor based on an organic heterostructure
Authors: Rost Constance , Gundlach David J. , Karg Siegfried , Rieß Walter
Published: April 2004

Ambipolar charge injection and transport are a prerequisite for a light-emitting organic fieldeffect transistor (OFET). Organic materials, however, typically show unipolar charge-carrier transport characteristics. Consequently, organic thin-film field-effect transistors based on a single material as active layer can typically either be operated as p- or as n-channel device. In this article we show that by using a heterostructure with pentacene as hole-transport and N,N′-Ditridecylperylene-3,4,9,10-tetracarboxylic diimide (PTCDI-C13H27) as electron-transport material, ambipolar characteristics, i.e., simultaneous p- and n-channel formation, can be observed in a single device. An OFET structure is investigated in which electrons and holes are injected from Mg top and Au bottom contacts into the PTCDI-C13H27 and pentacene layers, respectively. Our device exhibits electron and hole mobilities of 3×10−3 and 1×10−4 cm2/V s, respectively. This device architecture serves as a model structure for ambipolar field-effect transistors, which are a prerequisite for light-emitting field-effect transistors.
The scaling of embedded collisionless reconnection
Authors: Shay M. A. , Drake J. F. , Swisdak M. , Rogers B. N.
Published: April 2004

The scaling of the reconnection rate is examined in situations in which the equilibrium current supporting a reversed magnetic field has a spatial scale length that is much greater than all nonmagnetohydrodynamic (non-MHD) kinetic scales. In this case, denoted as embedded reconnection, the narrow non-MHD region around the x-line where dissipation is important is embedded inside of a much larger equilibrium current sheet. In this system, the magnetic field just upstream of this non-MHD region, Bd, changes significantly during the reconnection process. This wide equilibrium current sheet is contrasted with the very thin equilibrium current sheets of width c/ωpi used in previous simulations to establish the importance of the Hall term in Ohm’s law in allowing fast reconnection in large scale collisionless systems. In the present study we lay out a procedure for determining Bd directly from simulation data and use this value to renormalize the reconnection rate using Sweet–Parker-like scaling arguments. Using two-dimensional two-fluid simulations, we find that the time evolution of the reconnection process can be broken into two phases: A developmental phase that is quite long and strongly dependent on system size and presumably the dissipation mechanisms, and a fast asymptotic phase in which the flow velocity into the x-line is on the order of 0.1 of the Alfvén speed based on Bd. The reconnection rate during the asymptotic phase is independent of system size and the majority of island growth and flux reconnection occurs during this phase. The time to reconnect a significant amount of magnetic flux is roughly consistent with solar flare timescales.
Mechanism of ohmic behavior of Al/Ti contacts to p-type 4H-SiC after annealing
Authors: Johnson Brian J. , Capano Michael A.
Published: April 2004

We report on experiments to determine the mechanism of ohmic behavior of Al/Ti contacts to p-type SiC after thermal annealing. After ruling out heavy doping of the SiC surface due to diffusion of aluminum, and electric field enhancement due to surface morphology modification, we propose that the only remaining explanation is alloy formation at the metal–semiconductor interface. We present evidence from x-ray diffraction studies identifying these alloys as Ti3SiC2 and Al4C3, and review corroborating transmission electron microscopy studies. An alloy-assisted ohmic contact mechanism is presented and discussed.
Microstructural evidence of abnormal grain growth by solid-state wetting in Fe-3%Si steel
Authors: Park Hyun , Kim Doh-Yeon , Hwang Nong-Moon , Joo Young-Chang , Han Chan Hee , Kim Jae-Kwan
Published: April 2004

In this investigation, the mechanism of abnormal grain growth in Fe-3%Si steel was based on the microstructure evolution at the growth front of grains undergoing the abnormal growth. The most striking feature in the growth of abnormal grains was the penetration along the grain boundary of neighboring grains. This is energetically possible if the energy of the penetrated grain boundary is higher than the sum of the energy of two other grain boundaries shared by the penetrating abnormal grain. Along the growth front of an investigated abnormally growing grain, 15 out of 1381 triple junctions showed the clear microstructural evidence of the grain boundary penetration by the abnormal grain. Misorientation measurements of 34 penetrated grain boundaries using electron backscattered diffraction showed that not a single boundary has a low angle, implying that the penetrated grain boundaries have the high energy. These results are best explained by the abnormal grain growth with solid-state wetting.
Genetic variation for seed yield components in the birdsfoot trefoil cultivar, Grasslands Goldie
Authors: Kelman W. M. , Ayres J. F.
Published: April 2004

The persistence of hard-seeded perennial legumes can be facilitated by breeding and management programs that enhance seedling recruitment and maintain plant population density. In northern New South Wales, day length limits optimal flowering intensity and seed set of the otherwise promising birdsfoot trefoil cultivar, Grasslands Goldie (Lotus corniculatus L.). We studied the feasibility of improving flowering and seed production traits of this cultivar. To measure the extent of genetic variation for seed yield components, half-sib families derived from 45 parent plants collected from a population of cv. Goldie collected from Inverell, New South Wales were grown in the field at Glen Innes, NSW, and Canberra, ACT. Flowering time, flowering intensity and seed yield components (umbels per stem, pods per umbel, pods per stem, seeds per pod and seed mass) were recorded at both sites, while plant weight, height and width were also measured at the Canberra site. There was significant genetic variation among half-sib families and high narrow-sense heritabilities (on a family mean basis) for flowering time (0.73 ± 0.11), flowering intensity (0.66 ± 0.12) and plant height (0.78 ± 0.10). High estimates of narrow-sense heritability for seed yield components indicated that selection advance would be achieved under both sward and spaced plant conditions. There was evidence that selection for prolific flowering in cv. Grasslands Goldie was associated in the progeny populations with an increase in the number of umbels per stem. This component is a readily measured indicator of flowering intensity and should prove useful in developing more prolific and persistent populations from further selection within cv. Goldie and other birdsfoot trefoil populations.
DNA end joining becomes less efficient and more error-prone during cellular senescence
Authors: Seluanov Andrei , Mittelman David , Pereira-Smith Olivia M. , Wilson John H. , Gorbunova Vera
Published: April 2004

Accumulation of somatic mutations is thought to contribute to the aging process. Genomic instability has been shown to increase during aging, suggesting an aberrant function of DNA double-strand break (DSB) repair. Surprisingly, DSB repair has not been examined with respect to cellular senescence. Therefore, we have studied the ability of young, presenescent, and senescent normal human fibroblasts to repair DSBs in transfected DNA by using a fluorescent reporter substrate. We have found that the efficiency of end joining is reduced up to 4.5 fold in presenescent and senescent cells, relative to young cells. Sequence analysis of end junctions showed that the frequency of precise ligation was higher in young cells, whereas end joining in old cells was associated with extended deletions. These results indicate that end joining becomes inefficient and more error-prone during cellular senescence. Furthermore, the ability to use microhomologies for end joining was compromised in senescent cells, suggesting that young and senescent cells may use different end joining pathways. We hypothesize that inefficient and aberrant end joining is a likely mechanism underlying the age-related genomic instability and higher incidence of cancer in the elderly.
Dual–Task Slowing and the Effects of Cross–Task Compatibility
Authors: Azuma Rayna , Prinz Wolfgang , Koch Iring
Published: April 2004

Recent studies have shown that visual encoding requires central processing, evidenced in the form of dual–task interference on response processes of a reaction time (RT) task. We report two experiments examining such dual–task interference: (1) at global level, to establish that visual encoding indeed requires central processing; and (2) at code level, to see whether two tasks may share the same representational codes. To this end, we manipulated the compatibility relation between the response codes for an auditory choice RTtask and the stimulus codes for a logically independent visual motion detection task. The results showed significant dual–task slowing of the response for the auditory task, demonstrating the interference at a global level. The effects of cross–task compatibility (CTC) were obtained at the short stimulus onset asynchrony (SOA), showing that the RTs were faster for compatible trials. Furthermore, the CTC effect remained even when the visual stimulus did not need to be “consolidated” (Jolicoeur & Dell'Acqua, 1998) for reporting, while the response postponement effect was greatly reduced. We interpret these results as indicating that the present two tasks share both “central” processes and common representational codes, but that these two levels of dual–task interference can be dissociated.
Book Review: Levels of processing 30 Years on [Special Issue of Memory]
Authors: Lovie Sandy
Published: April 2004

There is no abstract for this publication
Parieto–Occipital Areas Involved in Efficient Filtering in Search: A Time Course Analysis of Visual Marking using Behavioural and Functional Imaging Procedures
Authors: Humphreys Glyn W , Kyllingsbæk Søren , Watson Derrick G. , Olivers Chris N. L. , Law Ian , Paulson Olaf B.
Published: April 2004

Search for a colour–form conjunction target can be facilitated by presenting one set of distractors prior to the second set of distractors and the target: the preview benefit (Watson & Humphreys, 1997). The early presentation of one set of distractors enables them to be efficiently filtered from search. We report two studies investigating the time course of the preview benefit. In Experiment 1 we use a standard reaction time analysis to show that the benefit has a relatively slow time course; old items need to precede the new set by 600 ms or more in order to be fully filtered from search. Furthermore, the reductions in reaction time across time in the preview condition varied nonlinearly with the display size, suggesting that old items were discounted from search in parallel. In Experiment 2 we examined the neural locus of this filtering effect over time, using positron emission tomography (PET). We show that regions of parieto–occipital cortex are selectively activated in a preview search condition relative to a detection baseline. These regions also increase in activation as the preview interval increases (and search then becomes easier), consistent with them modulating the parallel filtering of distractors from targets in spatial search. Interestingly, the same areas as those activated in preview search were also active in conjunction search relative to its own detection baseline. Thus these regions either modulate parallel filtering in conjunction search too, or they modulate different behavioural functions according to task constraints.
C‐peptide and Retinal Microangiopathy in Diabetes
Authors: Chakrabarti Subrata , Khan Zia Ali , Cukiernik Mark , Zhang Weixian , Sima Anders A. F.
Published: April 2004

Increased extracellular matrix (ECM) protein deposition
and capillary basement membrane (BM) thickening are
characteristic features of diabetic retinal microangiopathy.
Recent observations in the authors′ laboratories suggest
that high glucose in endothelial cells as well as diabetes
causes up‐regulation of total fibronectin (FN), as well as
extradomain‐B (EDB) containing the spliced variant of FN,
oncofetal FN, in the retina. This splice variant is normally
absent in mature adult tissues and is believed to be involved
in angiogenesis. In this study, the authors have investigated
the role of C‐peptide in the production of ECM
proteins and capillary BM thickening in the retina of diabetic
rats. They investigated retinas from poorly controlled
diabetic BB/Wor rats with or without C‐peptide treatment
as well as those from age‐matched nondiabetic control rats
after 8 months of diabetes. In addition, the authors investigated
retinas from BBDRZ/Wor rats, a model of type 2
diabetes. Following a treatment period of 8 months, retinal
tissues were harvested for gene expression and histological
analyses. In the retinas of diabetic BB/Wor rats, a
significant increase of oncofetal FN was demonstrated compared
to control rats. C‐peptide treatment of BB/Wor rats
completely prevented such increase. Furthermore, retinas
from BBDRZ/Wor rats, did not exhibit any such alteration
in oncofetal FN expression. The authors further examined retinal capillary BM thickening using ultrastructural
morphometry. C‐peptide treatment was ineffective in preventing
the diabetes‐induced increase in capillary BM thickness.
The authors′ previous studies of cultured endothelial
cells demonstrated that oncofetal FN synthesis is, at
least in part, mediated via transforming growth factor‐β
(TGF‐β) and endothelin‐1 (ET‐1). Hence, they examined
these two transcripts in the retina of these animals. Diabetes
caused significant increase in mRNA expression of ET‐1 and
TGF‐β, which was not prevented by C‐peptide treatment.
Hence it appears that C‐peptide is effective in preventing
diabetes‐induced oncofetal FN expression and that these effects
are not mediated via ET‐1 or TGF‐β. In conclusion,
these data suggest that C‐peptide is involved in regulating
ECM protein composition. Furthermore, normalization of
diabetes‐induced oncofetal FN up‐regulation may suggest
importance of C‐peptide in advanced alterations in diabetic
retinopathy such as angiogenesis.
Stratified or Comprehensive? The Economic Efficiency of School Design
Authors: Brunello Giorgio , Giannini Massimo
Published: April 2004

We study the efficiency of secondary school design by focusing on the degree of differentiation between vocational and general education. Using a simple model of endogenous job composition, we analyze the interaction between relative demand and relative supply of skills and characterize efficient school design when the government runs schools and cares about total net output. We show that neither a comprehensive nor a stratified system unambiguously dominates the other system in terms of efficiency for all possibile values of the underlying parameters. Since comprehensive systems generate more equal labour market outcomes, it follows that the relationship between efficiency and equity in secondary education is not necessarily a trade off.
Identifying Earnings Assimilation of Immigrants under Changing Macroeconomic Conditions
Authors: Barth Erling , Bratsberg Bernt , Raaum Oddbjørn
Published: April 2004

Failure to account for differences between immigrants and natives in their responsiveness to changes in macroeconomic conditions may bias estimates of assimilation effects on immigrant earnings. Using Norwegian register data from 1980 to 1996, we first establish that earnings of immigrants from non‐OECD countries exhibit greater sensitivity to local unemployment than do earnings of natives. The empirical analysis further reveals that standard methods of estimation—which fail to consider differential immigrant and native responsiveness—understate earnings growth and overstate cohort differentials among non‐OECD immigrants. These biases are attributable to trends in macroeconomic conditions over the sample period.
Dissociating brain regions controlling the temporal and ordinal structure of learned movement sequences
Authors: Bengtsson Sara L. , Ehrsson H. Henrik , Forssberg Hans , Ullén Fredrik
Published: April 2004

We used functional magnetic resonance imaging to investigate if different brain regions are controlling the temporal and ordinal structure of movement sequences during performance. Human subjects performed overlearned spatiotemporal sequences of key‐presses using the right index finger. Under different conditions, the temporal and the ordinal structure of the sequences were varied systematically in relation to each other, using a factorial design: COMBINED had a rhythm of eight temporal intervals and a serial order of eight keys; TEMPORAL had an eight‐interval rhythm produced on one key; ORDINAL had an isochronous rhythm and an eight‐key serial order; two control conditions had an isochronous pulse performed on one or two keys, respectively. Brain regions involved in rhythmic and ordinal control of the sequences were revealed by analysing main effect contrasts for the corresponding factors. TEMPORAL and ORDINAL were also compared directly to test for significant differences. A dissociation was found between largely the presupplementary motor area, the right inferior frontal gyrus and precentral sulcus, and the bilateral superior temporal gyri, involved in temporal control, and lateral fronto‐parietal areas, the basal ganglia and the cerebellum, which were implicated in ordinal control. The vermis and the superior colliculus were the only regions with an activity increase specifically related to combining long temporal and ordinal sequences. We conclude that humans use different brain networks for temporal and ordinal sequence control, and that the performance of combined sequences activates both networks, the medial cerebellum, and the superior colliculus.
Humanin antagonists: mutants that interfere with dimerization inhibit neuroprotection by Humanin
Authors: Hashimoto Yuichi , Terashita Kenzo , Niikura Takako , Yamagishi Yohichi , Ishizaka Miho , Kanekura Kohsuke , Chiba Tomohiro , Yamada Marina , Kita Yoshiko , Aiso Sadakazu , Matsuoka Masaaki , Nishimoto Ikuo
Published: April 2004

The 24‐residue peptide Humanin (HN) protects neuronal cells from insults of various Alzheimer's disease (AD) genes and Aβ by forming a homodimer. We have previously shown that P3A, S7A, C8A, L9A, L12A, T13A, S14A and P19A mutations nullify the neuroprotective function of HN [Yamagishi, Y., Hashimoto, Y., Niikura, T. & Nishimoto, I. (2003) Peptides, 24, 585–595]. Here we examined whether any of these ‘null’ mutants could function as dominant‐negative mutants. Homodimerization‐defective mutants, P3A‐, L12A‐, S14A‐ and P19A‐HN, specifically blocked neuroprotection by HN, but not by activity‐dependent neurotrophic factor. Furthermore, insertion of S7A, the mutation that blocks the homodimerization of HN, but not insertion of G5A abolished the antagonizing function of L12A‐HN. While L12A‐HN and G5A/L12A‐HN actually inhibited HN homodimerization, S7A/L12A‐HN had no effect. These data indicate that P3A‐, L12A‐, S14A‐ and P19A‐HN function as HN antagonists by forming an inactive dimer with HN. This study provides a novel insight into the understanding of the in vivo function of HN, as well as into the development of clinically applicable HN neutralizers.
Modulation of AMPA currents by D2 dopamine receptors in striatal medium‐sized spiny neurons: are dendrites necessary?
Authors: Hernández‐Echeagaray Elizabeth , Starling Amaal J. , Cepeda Carlos , Levine Michael S.
Published: April 2004

Glutamatergic afferents from the neocortex constitute the major excitatory input to striatal medium‐sized spiny neurons (MSNs). Glutamate's actions on MSNs are modulated by dopamine (DA) through D1 and D2 receptor families. Although D1 modulation of glutamate responses has been well‐characterized, the contribution of postsynaptic D2 receptors to α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) responses has not been studied extensively. We examined DA modulation of AMPA currents using whole‐cell voltage‐clamp recordings of MSNs acutely dissociated and in slices. In dissociated cells, the D2 agonist quinpirole (10 µm) produced small and inconsistent effects on AMPA currents. The magnitude of the current, as well as its modulation by quinpirole, was related to the dendritic elaboration of the dissociated cell. Thus, quinpirole altered AMPA currents only slightly when few initial dendritic segments were present. The amplitude of the current was greater and quinpirole consistently decreased this current in dissociated cells displaying at least three primary dendrites and several secondary and tertiary dendrites. Cyclothiazide, a compound that prevents AMPA receptor desensitization, greatly increased AMPA currents. In the presence of cyclothiazide, quinpirole also consistently reduced AMPA currents. Finally, in slices, AMPA current amplitude was always reduced after application of quinpirole. Sulpiride, a D2 antagonist, prevented attenuation of AMPA currents in both acutely dissociated neurons and neurons in slices. These results provide evidence that AMPA currents are attenuated by DA via activation of postsynaptic D2 receptors. In addition, they indicate that the dendrites and/or the amplitude of the current are important variables for DA modulation of AMPA currents in MSNs.
AMPA receptor‐mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanisms
Authors: Satake Shin'Ichiro , Saitow Fumihito , Rusakov Dmitri , Konishi Shiro
Published: April 2004

A major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand‐gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic inhibition of GABAergic transmission onto Purkinje cells in the cerebellar cortex. Although presynaptic inhibition is critical for information processing at central synapses, the molecular mechanisms by which AMPARs take part in such actions are not known. This study therefore aimed at further examining the properties of AMPAR‐mediated presynaptic inhibition at GABAergic synapses in the rat cerebellum. Our data provide evidence that the climbing fibre‐induced inhibition of GABA release from interneurons depends on AMPAR‐mediated activation of GTP‐binding proteins coupled with down‐regulation of presynaptic voltage‐dependent Ca2+ channels. A Gi/o‐protein inhibitor, N‐ethylmaleimide, selectively abolished the AMPAR‐mediated presynaptic inhibition at cerebellar GABAergic synapses but did not affect AMPAR‐mediated excitatory actions on Purkinje cells. Furthermore, both Gi/o‐coupled receptor agonists, baclofen and DCG‐IV, and the P/Q‐type calcium channel blocker ω‐agatoxin IVA markedly occluded the AMPAR‐mediated inhibition of GABAergic transmission. Conversely, AMPAR activation inhibited action potential‐triggered Ca2+ influx into individual axonal boutons of cerebellar GABAergic interneurons. By suppressing the inhibitory inputs to Purkinje cells, the AMPAR‐mediated presynaptic inhibition could thus provide a feed‐forward mechanism for the information flow from the cerebellar cortex.
Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection*
Authors: Hellberg Å. , Ringressi A. , Yahalom V. , Säfwenberg J. , Reid M. E. , Olsson M. L.
Published: April 2004

The aim of this study was to further explore the molecular genetic bases of the clinically important but rare blood group phenotypes p, P1k and P2k by analysis of the 4‐α‐galactosyltransferase (Pk) and 3‐β‐N‐acetylgalactosaminyltransferase (P) genes responsible for synthesis of the related Pk (Gb3) and P (Gb4) antigens respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against certain infectious agents. Blood samples from 20 p and 11 P1k or P2k individuals of different geographic and ethnic origin were investigated. DNA sequencing by capillary electrophoresis was performed following amplification of the coding regions in the Pk or P genes. In the Pk gene, nine novel and five previously described mutations were detected. One of the newly found mutations introduced an immediate stop, five shifted the reading frame introducing premature stop codons and three were missense mutations causing amino acid substitutions in conserved regions of the transferase. Four new and two previously described mutations in the P gene were found. Three of the novel alleles reported here carried nonsense mutations whilst the fourth allele had a missense mutation. The finding of 13 novel mutations in 14 alleles emphasizes further the genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.
FLT‐3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact
Authors: Au Wing Y. , Fung Alvin , Chim Chor S. , Lie Albert K. , Liang Raymond , Ma Edmond S. K. , Chan Cheuk H. , Wong Kit F. , Kwong Yok L.
Published: April 2004

FLT‐3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation‐loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT‐3 aberrations in a cohort of APL patients. FLT‐3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the ITD was recognized as an increase in the size of the PCR product. FLT‐3 exon  17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT‐3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835 mutation: 1). FLT‐3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT‐3 ITD to be associated with non‐remission (P = 0·06). For disease‐free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT‐3 ITD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT‐3 inhibitors in the treatment of APL.
Prophylactic effect of recombinant factor VIIa in factor VII deficient patients
Authors: Mathijssen Natascha C. J. , Masereeuw Rosalinde , Verbeek Kitty , Maurice Lavergne J. , Costa Jean‐Marc , Van Heerde Waander L. , Nováková Irena R. O.
Published: April 2004

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder associated with a bleeding tendency. We describe three patients with congenital FVII deficiency who have been treated with activated recombinant factor VII (rVIIa). Two patients had novel mutations and were treated prophylactically with 1·2 mg rVIIa two to three times a week. Patients 1 and 2 had a severe bleeding tendency. The frequency and severity of bleeding decreased by treatment with rVIIa compared with similar treatment with plasma‐derived FVII. The third patient with a moderate bleeding phenotype was treated on demand and showed no change in the frequency of bleeding upon treatment with rVIIa or plasma products. The beneficial effect of rVIIa cannot be explained by the rVIIa half‐lives. Pharmacokinetical analysis showed rVIIa activity half‐lives of 35, 50 and 54 min for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of FVII deficient patients with rVIIa appears to be applicable, safe and successful, although the mechanism of action remains to be elucidated.
Urocortin III, A Brain Neuropeptide of the Corticotropin‐Releasing Hormone Family: Modulation by Stress and Attenuation of Some Anxiety‐Like Behaviours
Authors: Venihaki M. , Sakihara S. , Subramanian S. , Dikkes P. , Weninger S. C. , Liapakis G. , Graf T. , Majzoub J. A.
Published: April 2004

Following its discovery 20 years ago, corticotropin‐releasing hormone (CRH) has been postulated to mediate both hormonal and behavioural responses to stressors. Here, we characterize and describe a behavioural role for the murine gene, UcnIII, which encodes a recently discovered CRH‐related neuropeptide, urocortin III. We found that mouse UcnIII is expressed predominantly in regions of the brain known to be involved in stress‐related behaviours, and its expression in the hypothalamus increases following restraint. In addition, we found that intracerebroventricular administration of mUcnIII stimulates behaviours that are associated with reduced anxiety, including exploration of an open field and decreased latency to enter the lit compartment of a dark‐light chamber, but has no effect on the elevated‐plus maze. Finally, we found that mUcnIII does not exert any effects on the hormonal stress response. Based upon our findings, UcnIII may be an endogenous brain neuropeptide that is modulated by stress and stimulates behaviours associated with reduced anxiety. In this capacity, UcnIII may attenuate stress‐related behaviours, which may be useful both to help cope with stressful situations as well as to avoid pathology associated with excessive reaction to stressors.
Modulation of Oestrogen Receptor‐β mRNA Expression in Rat Paraventricular and Supraoptic Nucleus Neurones Following Adrenal Steroid Manipulation and Hyperosmotic Stimulation
Authors: Somponpun S. J. , Holmes M. C. , Seckl J. R. , Russell J. A.
Published: April 2004

Magnocellular neurosecretory neurones in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei express oestrogen receptor β (ERβ) but not ERα. In the PVN, ERβ is strongly expressed in the ventromedial parvocellular neurones projecting to the brainstem. We used quantitative in situ hybridization, with 35S‐labelled riboprobes, to study heterologous regulation by manipulating adrenal steroid hormones (72 h after adrenalectomy ± corticosterone replacement; repeated stress: halothane inhalation, environmental cold, immobilization, each daily for 3 days) in male rats. Adrenalectomy increased ERβ mRNA expression in the magnocellular PVN and SON, by 2.2 and 2.5‐fold, respectively, with no effect in the ventromedial parvocellular PVN neurones. Corticosterone replacement partially prevented the increases in ERβ mRNA expression in magnocellular PVN and SON neurones. Repeated stress over 72 h had no effect on ERβ mRNA expression in the magnocellular PVN or SON, but increased expression 1.4‐fold in the ventromedial parvocellular PVN neurones. Although consequences of hydromineral balance derangement after adrenalectomy may stimulate magnocellular neurones, strongly stimulating the neurones by giving intact male rats 2% saline to drink for 72 h decreased ERβ mRNA expression in the magnocellular PVN and SON neurones by approximately 60%, and in the ventromedial parvocellular PVN neurones by 13%. Thus, ERβ mRNA expression is negatively regulated by basal glucocorticoid secretion in magnocellular PVN and SON neurones, and positively regulated by stress in ventromedial parvocellular PVN neurones. However, ERβ mRNA expression in magnocellular neurones is negatively linked to hyperosmotic stimulation of the neurones. The 6.25‐fold variation in ERβ mRNA expression in magnocellular neurones from salt‐loading to adrenalectomy could alter their sensitivity to oestrogens. Consequently, regulation of oxytocin and vasopressin neurone activity via ERβ is expected to vary according to their functional state and, in particular, on basal glucocorticoid actions.
Prevention of hepatitis C virus infection*
Authors: Kew M. , François G. , Lavanchy D. , Margolis H. , Van Damme P. , Grob P. , Hallauer J. , Shouval D. , Leroux‐Roels G. , Meheus A.
Published: April 2004

In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13–14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations.
Infection with human herpes virus type 8 in an area at high prevalence for hepatitis C virus infection in southern Italy
Authors: Montella M. , Serraino D. , Crispo A. , Romano N. , Fusco M. , Goedert J. J.
Published: April 2004

Summary.  The Campania Region is a geographical area of southern Italy characterized by high incidence rates of hepatocellular carcinoma and of classic Kaposi's sarcoma. Epidemiological investigations carried out among different population groups in this region have found high prevalence rates of both hepatitis C virus (HCV) and human herpesvirus type 8 (HHV‐8). To assess co‐infection rates of HCV and HHV‐8, we carried out a cross‐sectional seroepidemiological study prevalence in Pomigliano d'Arco, a Health District of Campania located 20 km away from Naples. The overall rate of HCV/HHV‐8 co‐infection was 3.1%, 3.5% among men and 2.7% among women. No difference emerged in the HCV/HHV‐8 co‐infection rates according to seropositivity for HCV infection, either overall (Mantel Haenszel odds ratio = 1.2, 95% CI: 0.6–2.6) or when the analysis was stratified by gender. These findings support the hypothesis that in Campania common routes of transmission are rarely shared by HCV and HHV‐8 infections. Local factors may result in different epidemiological patterns for these two viral infections. However, our findings have important public health implications, especially in Mediterranean countries where HCV and HHV‐8 infections are endemic.
Polymorphisms of NS5B protein relates to early clearance of hepatitis C virus by interferon plus ribavirin: a pilot study
Authors: Kumagai N. , Takahashi N. , Kinoshita M. , Tsunematsu S. , Tsuchimoto K. , Saito H. , Ishii H.
Published: April 2004

Summary.  Although randomized trials have shown enhancement of efficacy for combination therapy with interferon (IFN) α‐2b and ribavirin compared with IFN monotherapy as first‐line treatment for chronic hepatitis C, infection with genotype 1b and high viremia are still associated with significantly low response rates compared with non‐1 genotypes and low viremia. We analysed amino acid sequences of the viral RNA‐dependent RNA polymerase (RdRP) or nonstructural protein 5B (NS5B), responsible for ribavirin misincorporation into RNA products in patients with genotype 1b‐related chronic hepatitis C and high viremia, and examined the relationship between such RdRp polymorphisms, and the initial decline in viral load induced by combination therapy with IFN‐α and ribavirin. Substitution of glutamic acid to lysine at the 124th position (E124K) and of isoleucine to valine at the 85th position (I85V) were found to be closely associated with a potent decline of viral load and viral clearance at 8 weeks of treatment (five of five patients, coincidence rate 100%). In conclusion, our results suggest that the polymorphisms of E124K and I85V identified in NS5B protein are crucial for early viral clearance in patients with genotype 1b and high viremia by combination therapy with IFN and ribavirin, and that detection of amino acid sequence motifs might enable prediction of clinical efficacy.
Why is psoriasis uncommon in Africans? The influence of dietary factors on the expression of psoriasis
Authors: Namazi M. R.
Published: April 2004

Psoriasis is uncommonly seen in Africans, probably partly due to genetic factors. However, the dietary habits of Africans may provide another explanation, which is explored in this paper. Maize, the staple diet in most parts of Africa, is high in linoleic acid but low in other polyunstaturated fatty acids and riboflavin. Linoleic acid is a precursor of prostaglandin E2 (PGE2) and its high intake, especially in the absence of other polyunsaturated fatty acids (PUFAs) and riboflavin, results in high tissue production of PGE2. PGE2 is known to suppress cellular immunity, resulting in decreased expression of psoriasis.
Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study
Authors: Adler Caleb M , Holland Scott K , Schmithorst Vince , Wilke Marko , Weiss Kenneth L , Pan Hai , Strakowski Stephen M
Published: April 2004

Objectives:  Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder.

Methods:  Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups.

Results:  The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high‐medium to large effect sizes. No significant group differences were identified in TADC.

Conclusions:  Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.
Menstrually related symptom changes in women with treatment‐responsive bipolar disorder
Authors: Karadag Figen , Akdeniz Fisun , Erten Evrim , Pirildar Sebnem , Yucel Basak , Polat Aslihan , Atmaca Murad
Published: April 2004

Objective:  In the present study, we aimed to evaluate menstrually related symptom changes in euthymic women with treatment‐responsive bipolar disorder (BD) compared with healthy control subjects and investigate the presence of premenstrual dysphoric disorder (PMDD).

Methods:  Thirty‐four euthymic women with treatment‐responsive BD on mood‐stabilizers (lithium and/or valproate) for at least 6 months and 35 control subjects with no history of medical/mental disorder between ages of 18 and 35 years with regular menstrual cycles were prospectively followed up for at least two consecutive menstrual cycles using the Daily Record of Severity of Problems‐Short Form (DRSP). Each subject was administered the retrospective self‐report questionnaire, Premenstrual Assessment Form (PAF), in the first postmenstrual phase of the menstrual cycle. Venous blood samples were collected between 19 and 22 days of menstrual cycle to evaluate ovulation by measuring the serum progesterone levels.

Results:  The differences in mean age, age of onset of menses, cycle length and bleeding length did not appear to be significantly meaningful between groups. In the retrospective assessment of premenstrual symptom changes, controls complained more than women with BD. More controls showed a 30% change in DRSP and in depressive and physical sub‐groups than the women with BD. Controls demonstrated a significant increase compared with treatment‐responsive BD patients in total, depressive, anxiety and attention sub‐group scores of DRSP from the postmenstrual to the premenstrual phase, whereas the scores of vegetative symptoms of controls and women with BD did not differ significantly during one cycle or both. Significant menstrual cycle effect was observed in both groups.

Conclusion:  Within the limitations of the study, the results suggest that ongoing mood‐stabilizing treatment may have a prophylactic effect against premenstrual symptom changes in women with treatment‐responsive BD.
The Impact of European Works Councils on Management Decision‐Making in UK and US‐based Multinationals: A Case Study Comparison
Authors: Marginson Paul , Hall Mark , Hoffmann Aline , Müller Torsten
Published: April 2004

The operation of European Works Councils (EWCs) is taking management and employee representatives in MNCs into uncharted territory. In particular, for companies headquartered in Anglo‐Saxon economies there is little domestic tradition of statutory employee consultation. Drawing on comparative case studies, this article investigates the impact of EWCs on the process and outcomes of corporate‐level management decision‐making in UK and US‐based MNCs. Variation in EWC impact arises from the interaction of structural factors, such as business focus, management organisation and pre‐existing industrial relations arrangements, and agency factors, including management policy and the cohesion of employee representatives.
Local Participatory Democracy in Britain's Health Service: Innovation or Fragmentation of a Universal Citizenship?
Authors: Milewa Timothy
Published: April 2004

A political emphasis upon the devolution of governance and management in the British National Health Service has, since 1997, been paralleled by an apparent concern to reinvigorate patient and public involvement in aspects of planning and decision‐making. A quasi‐communitarian rhetoric and echoes of nineteenth‐century welfare mutualism have accompanied significant reform of arrangements for patient and public involvement. This article considers the degree to which this fusion of normative exhortation and structural reform heralds a marked evolution in the principles and practice of participatory democracy in the planning and governance of health care. The reforms, in historical perspective, appear to constitute a significant extension of the arenas within which citizens can explore and debate issues pertaining to the health service. But selective political recourse to quasi‐communitarian sentiment points to an embryonic policy discourse that links entitlements to obligations on the part of those reliant on the NHS. This may be of considerable significance in a system of health care to which entitlement has, historically, been cast as a right of citizenship.
Lone Parents and Civil Law: Their Experience of Problems and Their Advice‐seeking Behaviour
Authors: Buck Alexy , Pleasence Pascoe , Balmer Nigel , O'Grady Aoife , Genn Hazel
Published: April 2004

The percentage of dependent children living in lone‐parent families has more than tripled in Britain over the last 30 years. Though there is much diversity within this lone‐parent population, there are common experiences and characteristics. Lone‐parent families tend to be headed by women, to be poor, on benefits and experience problems with ill health and disability. This paper examines lone parenthood in the context of the experience of justiciable problems (problems for which there is a potential legal remedy), drawing upon a large‐scale survey of 5,611 people representative of the population of England and Wales. The survey included 223 lone parents, who were likely to be female, to be living in rented accommodation, to be on a low income, to be economically inactive and to be in receipt of benefits. Lone parents were significantly more likely than others to have experienced a justiciable problem. Lone parents sought advice for their problems more often than others, particularly from solicitors, even after controlling for problems experienced. Lone parents were more likely than others to receive legal‐aid funding. Lastly, lone parents found trying to resolve problems particularly stressful, though they tended to believe that their life had improved as a consequence of doing so.
From Impossible Words to Conceptual Structure: the Role of Structure and Processes in the Lexicon
Authors: Johnson Kent
Published: April 2004

Abstract: The structure of words is often thought to provide important evidence regarding the structure of concepts. At the same time, most contemporary linguists posit a great deal of structure in words. Such a trend makes some atomists about concepts uncomfortable. The details of linguistic methodology undermine several strategies for avoiding positing structure in words. I conclude by arguing that there is insufficient evidence to hold that word‐structure bears any interesting relation to the structure of concepts.