bluuebunny/crossref_metadata_2025 huggingface dataset:
A new interpretation of sea‐surface slope probability density functions
Authors: Plant William J.
Published: September 2003

Sea‐surface slope probability density functions, which are usually fitted to a Gram‐Charlier series, can be fit equally well by a bound wave/free wave model in which the distributions of bound and free waves are Gaussian. Bound waves are generated by longer waves on the surface and travel at nearly the phase speed of the long wave while free waves are generated directly by the wind and travel at their intrinsic phase speed. These two types of short surface waves can usually be separated in measurements that yield their velocities. The integrals over the two distributions yield the probabilities of finding bound or free waves on the surface. We show that the probability of finding bound waves on the ocean is comparable to that in a wind‐wave tank and much larger than the probability of whitecapping. The mean slopes of the two distributions yield the mean tilts of bound or free waves. We show that the mean tilt of the bound waves is similar to that in a wind‐wave tank and close to that necessary to explain Doppler shifts in microwave backscatter from the sea surface at high incidence angles. Finally, the widths of the two distributions yield the variance of sea‐surface slopes at the locations of bound and free waves. We show that these are larger at sea than in a wind‐wave tank, which explains why bound waves at sea have not been recognized previously in sea‐surface slope probability distributions.
3‐Aminopropanal is a lysosomotropic aldehyde that causes oxidative stress and apoptosis by rupturing lysosomes
Authors: YU ZHENGQUAN , LI WEI , BRUNK ULF T.
Published: September 2003

During cerebral ischemia and following trauma, potent cytotoxic polyamine‐derived aminoaldehydes form, diffuse, and damage adjacent tissues not directly subjected to the initial insult. One such aldehyde is 3‐aminopropanal (3‐AP). The mechanisms by which such a small aldehydic compound is excessively cytotoxic have been unclear until recently when we showed that 3‐AP, having the structure of a weak lysosomotropic base, concentrates within the acidic vacuolar compartment and causes lysosomal rupture that, in turn, induces caspase activation and apoptotic cell death. Here, using cultured J774 cells and 3‐AP as a way to selectively burst lysosomes, we show that moderate lysosomal rupture induces a transient wave of oxidative stress. The start of this oxidative stress period is concomitant with a short period of enhanced mitochondrial membrane potential that later fades and is replaced by a decreased potential before the oxidative stress diminishes. The result of the study suggests that oxidative stress, which has often been described during apoptosis induced by agonists other than oxidative stress per se, may be a consequence of lysosomal rupture with direct and/or indirect effects on mitochondrial respiration and electron transport causing a period of passing enhanced formation of reactive oxygen species.
The organization of the microbial biodegradation network from a systems‐biology perspective
Authors: Pazos Florencio , Valencia Alfonso , De Lorenzo Víctor
Published: September 2003

Microbial biodegradation of environmental pollutants is a field of growing importance because of its potential use in bioremediation and biocatalysis. We have studied the characteristics of the global biodegradation network that is brought about by all the known chemical reactions that are implicated in this process, regardless of their microbial hosts. This combination produces an efficient and integrated suprametabolism, with properties similar to those that define metabolic networks in single organisms. The characteristics of this network support an evolutionary scenario in which the reactions evolved outwards from the central metabolism. The properties of the global biodegradation network have implications for predicting the fate of current and future environmental pollutants.
Directed expression of the HIV‐1 accessory protein Vpu in Drosophila fat‐body cells inhibits Toll‐dependent immune responses
Authors: Leulier François , Marchal Christelle , Miletich Isabelle , Limbourg‐Bouchon Bernadette , Benarous Richard , Lemaitre Bruno
Published: September 2003

Human immunodeficiency virus 1 (HIV‐1) expresses several accessory proteins that manipulate various host‐cell processes to achieve optimum replicative efficiency. One of them, viral protein U (Vpu), has been shown to interfere with the cellular degradation machinery through interaction with SCFβ‐TrCP complexes. To learn more about Vpu function in vivo, we used the genetically tractable fruit fly, Drosophila melanogaster. Our results show that the directed expression of Vpu, but not the non‐phosphorylated form, Vpu2/6, in fat‐body cells affects Drosophila antimicrobial responses. In flies, the Toll and Imd pathways regulate antimicrobial‐peptide gene expression. We show that Vpu specifically affects Toll pathway activation by inhibiting Cactus degradation. Given the conservation of the Toll/nuclear factor‐κB (NF‐κB) signalling pathways between flies and mammals, our results suggest a function for Vpu in the inhibition of host NF‐κB‐mediated innate immune defences and provide a powerful genetic approach for studying Vpu inhibition of NF‐κB signalling in vivo.
What is the role of serology in assessing Helicobacter pylori eradication?
Authors: Bergey B. , Marchildon P. , Peacock J. , Mégraud F.
Published: September 2003

Aim : To assess the decline in Helicobacter pylori antibodies after eradication of infection.

Methods : The H. pylori status was determined at entry (D0) by culture and histology performed on antral biopsies and after eradication treatment at day 42 (day 42) and after 6 months (M6) by the 13C‐urea breath test. The EIA kits used to determine the anti‐H. pylori antibody titre were HM‐CAP (immunoglobulin‐G) and PP‐CAP (immunoglobulin‐A) kits (Enteric Products, Inc.) and Pyloriset EIA‐G (Orion Diagnostica).

Results : Ninety‐three patients were included. For 82 patients who were successfully treated, no kit was sufficiently accurate at D42 to show eradication. The antibody titre decreased for HM‐CAP, PP‐CAP and Pyloriset EIA‐G by a mean of 35.6%, 41.2% and 64.7% between D0 and M6, respectively. According to the cut‐off values defined by the manufacturers, 8.5% (PP‐CAP, Pyloriset EIA‐G) and 9.7% (HM‐CAP) of the patients became H. pylori negative at M6. Using a 25% decrease in antibody titre between D0 and M6 as a threshold for H. pylori eradication, specificity was 100% for HM‐CAP, 89.9% for Pyloriset EIA‐G and 100% for PP‐CAP, whereas the sensitivity was 76.8%, 98.8% and 72%, respectively.

Conclusion : An antibody titre decrease of 25% at M6 was found to be accurate in confirming H. pylori eradication.
Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes
Authors: Herrlin Karin , Yasui‐Furukori Norio , Tybring Gunnel , Widén Jolanta , Gustafsson Lars L. , Bertilsson Leif
Published: September 2003

Aims  To investigate pharmacokinetics of the enantiomers of citalopram (CT) and its metabolites desmethylcitalopram (DCT) and didesmethylcitalopram (DDCT) in Swedish healthy volunteers in relation to CYP2C19 and CYP2D6 geno‐ and phenotypes.

Methods  Racemic CT was given for seven days to panels with different genotypes and the following mephenytoin (Me) and debrisoquine (De) hydroxylation phenotypes: EMDe/EMMe, PMDe/EMMe, EMDe/PMMe (n = 6 in all groups), and one PMDe/PMMe subject. Blood sampling was carried out during day 7, and all urine was collected for 12 h after the last dose of CT.

Results  The AUC of S‐CT was significantly higher in the EMDe/PMMe panel compared to the EMDe/EMMe and PMDe/EMMe panels (P < 0.05), whereas the AUC of R‐CT did not differ between the panels. Similar differences, although they did not reach statistical significance, were noted for S‐DCT and R‐DCT. The enantiomers of DDCT were not quantifiable in PMDe, and there was no difference in DDCT enantiomer concentrations between the other two panels. A PMDe/PMMe subject stopped taking CT after five days due to severe adverse effects. Based on two time points, this subject had a very long CT half‐life of 95 h. The value of 1.0 for the S/R ratio of the CT trough in this subject was similar to the mean S/R CT trough ratio of the EMDe/PMMe panel, but higher than the S/R CT ratio of the EMDe/EMMe panel (0.56; 95% CI 0.49–0.63) and the PMDe/EMMe panel (0.44; 95% CI 0.31–0.57). Thus the latter two phenotypes eliminated S‐CT more rapidly via CYP2C19. An adverse effect described as an ‘alcohol hangover’ feeling was reported by one subject from each of the three panels. These individuals had the highest concentrations of both CT enantiomers.

Conclusions  The AUC of S‐, but not R‐(CT) was found to be significantly higher in PM of mephenytoin compared to EMs, PMs may need a lower dosage of CT.
Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor, omapatrilat in healthy subjects
Authors: Liao Wei‐chi , Vesterqvist Ole , Delaney Carol , Jemal Mohammed , Ferreira Irene , Ford Neville , Swanson Brian , Uderman Howard
Published: September 2003

Aims To determine the pharmacokinetics, pharmacodynamics and tolerability of omapatrilat, a vasopeptidase inhibitor, in healthy subjects.

Methods The effects of oral omapatrilat were evaluated in healthy men in two double‐blind, placebo‐controlled, dose‐escalation trials. In a single‐dose study, subjects received omapatrilat in doses of 2.5, 7.5, 25, 50, 125, 250, or 500 mg. In a multiple‐dose study, subjects received doses of 10, 25, 50, 75, or 125 mg daily for 10 days.

Results In the multiple‐dose study, peak plasma concentrations (Cmax = 10–895 ng ml−1;tmax = 0.5–2 h) of omapatrilat were attained rapidly. Omapatrilat exhibited a long effective half‐life (14–19 h), attaining steady state in 3–4 days. In the single‐dose study,Cmax(1–1009 ng ml−1) and AUC(0,t) (0.4–1891 ng ml–1 h) were linear but not dose proportional. In the multiple‐dose study, based on weighted least‐squares linear regression analysesvsdose,Cmaxbut not AUC(0,t) was linear at the lower doses on day 10. The lowest dose of omapatrilat (2.5 mg) almost completely inhibited (> 97%) serum angiotensin converting enzyme activity at 2 h after dosing. In the multiple dose study, angiotensin converting enzyme activity was inhibited by more than 80% 24 h after all doses of omapatrilat. Inhibition of neutral endopeptidase activity was shown by increases in the daily urinary excretion of atrial natriuretic peptide and cyclic guanosine monophosphate at doses of more than 7.5 and 25 mg, respectively. In the single dose study, omapatrilat increased the daily urinary excretion of atrial natriuretic peptide dose‐dependently from 10.8 ± 4.1 (± SD) ng 24 h−1in the placebo group to 60.0 ± 18.2 ng 24 h−1in the 500 mg group. Omapatrilat did not affect sodium and potassium excretion or urinary volume. Compared with placebo, omapatrilat produced a decrease in mean arterial pressure at 3 h after all doses in both the single‐ and multiple‐dose studies.

Conclusions Omapatrilat was generally well tolerated. The pharmacokinetic and pharmacodynamic effects of omapatrilat are consistent with once‐daily dosing.
Chest pain during use of bupropion as an aid in smoking cessation
Authors: De Graaf L. , Diemont W. L.
Published: September 2003

Aims  To investigate the cause of chest pain during the use of bupropion as an aid to stop smoking.

Methods  The Netherlands Pharmacovigilance Centre received 22 reports of chest pain, associated with the use of bupropion as an aid to smoking cessation. Additional information about long‐term follow up was collected to analyze whether these complaints herald manifest cardiac disease.

Results  All but one patient recovered after withdrawal of bupropion. Seven patients were additionally investigated and in six of them, a cardiac cause could be excluded. During long‐term follow‐up, no coronary heart diseases were diagnosed.

Conclusions  These reports indicate that chest pain seems to be associated with the use of bupropion, but its origin remains unclear.
Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity
Authors: Isbister Geoffrey K. , Hackett L. P. , Dawson Andrew H. , Whyte Ian M. , Smith Anthony J.
Published: September 2003

Aims  To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters.

Methods  All moclobemide overdoses presenting over a 10‐year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half‐lives were estimated.

Results  Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide‐alone overdoses (odds ratio 35, 95% confidence inteval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature> 38.5 °C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting ≥ 6 g vomited or had charcoal. The mean elimination half‐life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose‐dependent increase in half‐life.

Conclusions  The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half‐life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.
Mitogenic effects of phospholipase D and phosphatidic acid in transiently permeabilized astrocytes: effects of ethanol
Authors: Schatter Beate , Walev Ivan , Klein Jochen
Published: September 2003

Investigations of lipid‐mediated signalling pathways are often limited by a lack of methods for the intracellular delivery of lipid messengers. We established a procedure for the transient permeabilization of astrocytes by an oxygen‐insensitive mutant of streptolysin‐O (SLO) to investigate the participation of the phospholipase D (PLD) signalling pathway in astroglial cell proliferation. Exogenous PLD, when incubated in the presence of SLO, caused an increase in DNA synthesis (measured by thymidine incorporation) which was completely suppressed by ethanol (0.3%, v/v). In parallel experiments, phosphatidic acid also induced a dose‐dependent mitogenic response which, however, was not affected by the presence of ethanol. Phosphatidic acid was more effective in this assay than diacylglycerol but its effect was sensitive to the protein kinase inhibitor Ro 31‐8220. Our findings provide direct evidence that disruption of the PLD signalling pathway by ethanol is sufficient to suppress astroglial proliferation, an effect that might contribute to the inhibition of brain growth in alcoholic embryopathy.
Presence of functional ATP and dinucleotide receptors in glutamatergic synaptic terminals from rat midbrain
Authors: Gualix Javier , Gómez‐Villafuertes Rosa , Díaz‐Hernández Miguel , Miras‐Portugal M. Teresa
Published: September 2003

Glutamatergic terminals from rat midbrain were characterized by immunolocalization of synaptophysin and the vesicular glutamate transporters, either VGLUT1 or VGLUT2. Terminals containing these markers represent about 31% (VGLUT1) and 16% (VGLUT2) of the total synaptosomal population. VGLUT1‐positive glutamatergic terminals responded to ATP or P1,P 5‐di(adenosine‐5′) pentaphosphate (Ap5A) with an increase in the intrasynaptosomal calcium concentration as measured by a microfluorimetric technique in single synaptosomes. Roughly 20% of the VGLUT1‐positive terminals responded to ATP, 13% to Ap5A and 11% to both agonists. Finally 56% of the terminals labeled with the anti‐VGLUT1 antibody did not show any calcium increase in response to ATP or Ap5A. A similar response distribution was also observed in the VGLUT2‐positive terminals. The Ca2+ responses induced by ATP and Ap5A in the glutamatergic terminals could be selectively inhibited by pyridoxal phosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS, 80 µm) and P1,P 5‐di(inosine‐5′) pentaphosphate (Ip5I, 100 nm), respectively. Both ATP and Ap5A, once assayed in the presence of extrasynaptosomal calcium, were able to induce a concentration‐dependent glutamate release from synaptosomal populations, EC50 values being 21 µm and 38 µm for ATP and Ap5A, respectively. Specific inhibition of glutamate release was obtained with PPADS on the ATP effect and with Ip5I on the dinucleotide response, indicating that separate receptors mediate the secretory effects of both compounds.
Expression of Concern: Potent anti‐amyloidogenic and fibril‐destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease
Authors: Ono Kenjiro , Yoshiike Yuji , Takashima Akihiko , Hasegawa Kazuhiro , Naiki Hironobu , Yamada Masahito
Published: September 2003

Cerebral deposition of amyloid β‐peptide (Aβ) in the brain is an invariant feature of Alzheimer's disease (AD). A consistent protective effect of wine consumption on AD has been documented by epidemiological studies. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of wine‐related polyphenols (myricetin, morin, quercetin, kaempferol (+)‐catechin and (–)‐epicatechin) on the formation, extension, and destabilization of β‐amyloid fibrils (fAβ) at pH 7.5 at 37°C in vitro. All examined polyphenols dose‐dependently inhibited formation of fAβ from fresh Aβ(1–40) and Aβ(1–42), as well as their extension. Moreover, these polyphenols dose‐dependently destabilized preformed fAβs. The overall activity of the molecules examined was in the order of: myricetin = morin = quercetin > kaempferol > (+)‐catechin = (–)‐epicatechin. The effective concentrations (EC50) of myricetin, morin and quercetin for the formation, extension and destabilization of fAβs were in the order of 0.1–1 µm. In cell culture experiments, myricetin‐treated fAβ were suggested to be less toxic than intact fAβ, as demonstrated by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay. Although the mechanisms by which these polyphenols inhibit fAβ formation from Aβ, and destabilize pre‐formed fAβin vitro are still unclear, polyphenols could be a key molecule for the development of preventives and therapeutics for AD.
Effect of resuscitative mild hypothermia on glutamate and dopamine release, apoptosis and ischaemic brain damage in the endothelin‐1 rat model for focal cerebral ischaemia
Authors: Van Hemelrijck An , Vermijlen David , Hachimi‐Idrissi Said , Sarre Sophie , Ebinger Guy , Michotte Yvette
Published: September 2003

The relationship between glutamate and dopamine release, apoptosis and ischaemic damage was studied following induction of transient focal cerebral ischaemia under normothermic (37°C) and postischaemic (resuscitative) mild hypothermic (34°C for 2 h) conditions in sevoflurane anaesthetized male Wistar rats. Focal ischaemia was induced by infusing endothelin‐1 adjacent to the middle cerebral artery. In vivo microdialysis was used to sample glutamate and dopamine from striatum and parietal cortex of the ipsilateral hemisphere. The volume of ischaemic damage and the degree of apoptosis were determined 24 h after the insult. In both striatum and cortex of the normothermic group an initial increase in extracellular glutamate and dopamine levels following endothelin‐1 infusion was observed. Striatal glutamate levels remained enhanced (250% of baseline) throughout the experiment, while the other neurotransmitter levels returned to baseline values. Hypothermia significantly attenuated the endothelin‐1 induced glutamate release in the striatum. It also reduced apoptosis and infarct volume in the cortex. These results indicate that: (i) postischaemic mild hypothermia exerts its neuroprotective effect by inhibiting apoptosis in the ischaemic penumbral region; and (ii) this effect is not associated with an attenuation of glutamate or dopamine release in the cortex.
Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain‐derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting
Authors: Shetty Ashok K. , Zaman Vandana , Shetty Geetha A.
Published: September 2003

A significant upregulation of neurotrophins particularly brain‐derived neurotrophic factor (BDNF) is believed to be involved in the initiation of epileptogenic changes such as the aberrant axonal sprouting and synaptic reorganization in the injured hippocampus. However, it is unknown which of the neurotrophins are upregulated during the peak period of aberrant mossy fiber sprouting in the chronically injured hippocampus. We measured chronic changes in the levels of BDNF, nerve growth factor (NGF) and neurotrophin‐3 (NT‐3) in the adult hippocampus using enzyme‐linked immunosorbent assay (ELISA) after a unilateral intracerebroventricular administration of kainic acid (KA), a model of temporal lobe epilepsy. For comparison, neurotrophins were also measured from the control intact hippocampus. Further, to see the association between changes in neurotrophin levels and the progression of mossy fiber sprouting, chronic changes in the mossy fiber distribution within the dentate supragranular layer (DSGL) were quantified. In the KA‐lesioned hippocampus, the neurotrophins BDNF and NGF were upregulated at 4 days post‐lesion, in comparison to their levels in the intact hippocampus. However, the concentration of BDNF reached the baseline level at 45 days post‐lesion and dramatically diminished at 120 days post‐lesion. In contrast, the upregulation of NGF observed at 4 days post‐lesion was sustained at both 45 days and 120 days post‐lesion. The concentration of NT‐3 was upregulated at 45 days post‐lesion but remained comparable to baseline levels at 4 days and 120 days post‐lesion. Interestingly, analysis of mossy fiber sprouting revealed that most of the aberrant sprouting in the lesioned hippocampus occurs between 45 days and 120 days post‐lesion. Taken together, these results suggest that the period of robust mossy fiber sprouting does not correlate with the phase of post‐lesion BDNF upregulation. Rather, it shows a relationship with the time of upregulation of neurotrophins NGF and NT‐3.
Depletion of wild‐type huntingtin in mouse models of neurologic diseases
Authors: Zhang Yu , Li Mingwei , Drozda Martin , Chen Minghua , Ren Shengjun , Mejia Sanchez Rene O. , Leavitt Blair R. , Cattaneo Elena , Ferrante Robert J. , Hayden Michael R. , Friedlander Robert M.
Published: September 2003

Huntington's disease (HD) is caused by a mutation in the gene encoding for huntingtin resulting in selective neuronal degeneration. Because HD is an autosomal dominant disorder, affected individuals have one copy of the mutant and one copy of the wild‐type allele. Huntingtin has antiapoptotic properties and is critical for cell survival. However, the important role of wild‐type huntingtin in both HD and other neurological diseases has not been fully recognized. We demonstrate disease‐associated decreased levels of full‐length huntingtin in brains of transgenic mouse models of HD, ischemia, trauma, and in spinal cord after injury. In addition, overexpression of wild‐type huntingtin confers in vivo protection of neurodegeneration after ischemia. We propose that in HD, in addition to a toxic gain‐of‐function of mutant huntingtin, a parallel depletion of wild‐type huntingtin results in a detrimental loss‐of‐function, playing an important role in disease progression.
Glutamine efflux from astrocytes is mediated by multiple pathways
Authors: Deitmer Joachim W. , Bröer Angelika , Bröer Stefan
Published: September 2003

The neurotransmitter glutamate, once released into the synaptic cleft, is largely recycled by the glutamate–glutamine cycle, which involves uptake into astrocytes, conversion into glutamine and subsequent release of glutamine from astrocytes as a precursor for neuroneal glutamate synthesis. We analysed glutamine efflux from cultured astrocytes by pre‐loading cells with labelled glutamine for 30 min and subsequently measured glutamine efflux for 30 min. Efflux of pre‐loaded glutamine was rapid and almost complete after 30 min with a first order rate of 0.11 ± 0.01/min. Efflux was 50% reduced when cells were depleted of intracellular Na+. Increasing intracellular Na+ concentration had a small stimulatory effect on glutamine efflux, indicating the participation of a Na+‐dependent transport mechanism. About 50% of the basal efflux could not be inhibited by depletion of the intracellular Na+, suggesting the presence of an additional Na+‐independent transport mechanism. Glutamine efflux was stimulated two‐ to threefold by addition of extracellular neutral amino acids, such as alanine or leucine. The stimulatory effects of alanine and leucine had a Na+‐dependent and a Na+‐independent component, suggesting the presence of two antiport mechanisms one involving Na+. When compared to the expression of glutamine transporter mRNAs in cultured astrocytes it appeared likely that glutamine efflux was mediated by SN1, LAT2, ASCT2 and an additional, yet unidentified, transporter that mediates about 40% of the basal efflux.
Glutamate transport, glutamine synthetase and phosphate‐activated glutaminase in rat CNS white matter. A quantitative study
Authors: Hassel Bjørnar , Boldingh Karen Astrid , Narvesen Cecilie , Iversen Evy Grini , Skrede Knut Kristian
Published: September 2003

Glutamatergic signal transduction occurs in CNS white matter, but quantitative data on glutamate uptake and metabolism are lacking. We report that the level of the astrocytic glutamate transporter GLT in rat fimbria and corpus callosum was ∼ 35% of that in parietal cortex; uptake of [3H]glutamate was 24 and 43%, respectively, of the cortical value. In fimbria and corpus callosum levels of synaptic proteins, synapsin I and synaptophysin were 15–20% of those in cortex; the activities of glutamine synthetase and phosphate‐activated glutaminase, enzymes involved in metabolism of transmitter glutamate, were 11–25% of cortical values, and activities of aspartate and alanine aminotransferases were 50–70% of cortical values. The glutamate level in fimbria and corpus callosum was 5–6 nmol/mg tissue, half the cortical value. These data suggest a certain capacity for glutamatergic neurotransmission. In optic and trigeminal nerves, [3H]glutamate uptake was < 10% of the cortical uptake. Formation of [14C]glutamate from [U‐14C]glucose in fimbria and corpus callosum of awake rats was 30% of cortical values, in optic nerve it was 13%, illustrating extensive glutamate metabolism in white matter in vivo. Glutamate transporters in brain white matter may be important both physiologically and during energy failure when reversal of glutamate uptake may contribute to excitotoxicity.
Time‐dependent changes in gene expression profiles of midbrain dopamine neurons following haloperidol administration
Authors: Fasulo Wendy H. , Hemby Scott E.
Published: September 2003

Antipsychotic drugs require a treatment regimen of several weeks before clinical efficacy is achieved in patient populations. While the biochemical mechanisms underlying the delayed temporal profile remain unclear, molecular adaptations in specific neuroanatomical loci are likely involved. Haloperidol‐induced changes in gene expression in various brain regions have been observed; however, alterations in distinct neuronal populations have remained elusive. The present study examined changes in gene expression profiles of ventral tegmental area (VTA) and substantia nigra (SN) tyrosine hydroxylase immunopositive neurons following 1, 10 or 21 days of haloperidol administration (0.5 mg/kg/day). Macroarrays were used to study the expression of receptors, signaling proteins, transcription factors and pre‐ and post‐synaptic proteins. Data were analyzed using conventional statistical procedures as well as self‐organizing maps (SOM) to elucidate conserved patterns of expression changes. Results show statistically significant haloperidol‐induced and time‐dependent alterations in 17 genes in the VTA and 25 genes in the SN, including glutamate and GABA receptor subunits, signaling proteins and transcription factors. SOMs revealed distinct patterns of gene expression changes in response to haloperidol. Understanding how gene expression is altered over a clinically relevant time course of haloperidol administration may provide insight into the development of antipsychotic efficacy as well as the underlying pathology of schizophrenia.
Coherent vortex extraction in three-dimensional homogeneous turbulence: Comparison between CVS-wavelet and POD-Fourier decompositions
Authors: Farge Marie , Schneider Kai , Pellegrino Giulio , Wray Alan A. , Rogallo Robert S.
Published: September 2003

The coherent vortex simulation (CVS) decomposes each realization of a turbulent flow into two orthogonal components: An organized coherent flow and a random incoherent flow. They both contribute to all scales in the inertial range, but exhibit different statistical behaviors. The CVS decomposition is based on the nonlinear filtering of the vorticity field, projected onto an orthonormal wavelet basis made of compactly supported functions, and the computation of the induced velocity field using Biot–Savart’s relation. We apply it to a three-dimensional homogeneous isotropic turbulent flow with a Taylor microscale Reynolds number Rλ=168, computed by direct numerical simulation at resolution N=2563. Only 2.9%N wavelet modes correspond to the coherent flow made of vortex tubes, which contribute 99% of energy and 79% of enstrophy, and exhibit the same k−5/3 energy spectrum as the total flow. The remaining 97.1%N wavelet modes correspond to a incoherent random flow which is structureless, has an equipartition energy spectrum, and a Gaussian velocity probability distribution function (PDF). For the same flow and the same compression rate, the proper orthogonal decomposition (POD), which in this statistically homogeneous case degenerates into the Fourier basis, decomposes each flow realization into large scale and small scale flows, in a way similar to large eddy simulation (LES) filtering. It is shown that the large scale flow thus obtained does not extract the vortex tubes equally well as the coherent flow resulting from the CVS decomposition. Moreover, the small scale flow still contains coherent structures, and its velocity PDF is stretched exponential, while the incoherent flow is structureless, decorrelated, and its velocity PDF is Gaussian. Thus, modeling the effect of the incoherent flow discarded by CVS-wavelet shall be easier than modeling the effect of the small scale flow discarded by POD-Fourier or LES.
Molecular dynamics simulation of the inverted temperature gradient phenomenon
Authors: Meland Roar
Published: September 2003

A molecular dynamics simulation of the temperature profile between two liquid surfaces kept at slightly different temperatures, with evaporation from the hot surface and condensation on the cold surface, is presented. The more than 30 years old theoretical prediction of an inverted temperature gradient by gas–kinetic calculations has still not been proven experimentally. However, the inverted temperature gradient phenomenon is observed in the molecular dynamics simulation and the temperature profile agrees well with gas–kinetic theory. It should be stressed that the liquid is also simulated in molecular dynamics; distribution functions at the interfaces have not been specified as is necessary in kinetic theory calculations.
Thermocapillary flow and rupture in films of molten metal on a substrate
Authors: Ajaev Vladimir S. , Willis David A.
Published: September 2003

We consider fluid flow in thin films of molten metal resulting from irradiation by a Gaussian laser beam. Surface tension gradients due to nonuniform heating induce a flow of the molten liquid away from the center of the irradiated area, leading to formation of dry areas on the substrate. We develop a mathematical model of the flow under the assumption of the large ratio of laser beam radius to film thickness. The model extends the standard lubrication-type analysis to include the highly nonlinear dependence of evaporative flux on local interfacial temperature, unsteady heat conduction in the substrate, and positive disjoining pressure due to unbalanced contributions from the kinetic energy of free electrons in the metal. The latter is proportional to the inverse square of the film thickness. We identify thermocapillary stresses as the main mechanism of rapid removal of liquid metal from the irradiated area. Characteristic times of the process, as well as shapes of the molten region surface, agree with experimental observations. We investigate rupture of the molten film and find two different rupture scenarios. The melt surface can either touch the substrate at a point (point rupture) or along a line at a certain radial distance away from the center of the irradiated area (ring rupture). Nondimensional criteria for these two mechanisms are identified. In particular, we show that positive disjoining pressure promotes ring rupture.
Stark-shift modulation absorption spectroscopy of single quantum dots
Authors: Alén Benito , Bickel Florian , Karrai Khaled , Warburton Richard J. , Petroff Pierre M.
Published: September 2003

Excitonic interband optical transitions within single InAs self-assembled quantum dots have been directly observed in a transmission experiment at 4.2 K. Using Stark shift, the excitonic energy levels of a single quantum dot are tuned into resonance with a narrow-band laser line. The Stark shift is also modulated at low frequencies. Relative changes in transmission can be detected this way down to one part per million. The oscillator strength as well the homogeneous linewidth of the transition is obtained.
Determination of the electronic conductivity of polybithiophene films at different doping levels using in situ electrochemical impedance measurements
Authors: Garcia-Belmonte Germà , Bisquert Juan , Popkirov George S.
Published: September 2003

This letter presents in situ electronic conductivity measurements of polybithiophene films using a twin working electrode in an electrochemical configuration. A twin electrode is made of two metallic stripes which are separated by a few micrometers by an insulating gap. As the polymer doping level depends on the bias potential maintained between counter- and working electrodes, changes of electronic density of many orders of magnitude (from 1016 up to 1020 cm−3 in the potential window investigated) can be achieved using this experimental technique. A simple impedance model based on electronic (polaronic) diffusion between absorbing contacts accounts for the measured impedance spectra. The dependence of low-frequency conductivity σdc with bias potential E at low doping levels follows the relationship ln σdc∝E/2kBT, which allows one to regard it as a double contribution, simultaneously electronic and ionic, to the thermodynamics of doping. It has also been possible to calculate the electronic chemical diffusion coefficient from the diffusion characteristic frequency ωd, which results within the range of De∼4–1×10−3 cm2 s−1.
Orientation dependent microwave dielectric properties of ferroelectric Ba1−xSrxTiO3 thin films
Authors: Moon Seung Eon , Kim Eun-Kyoung , Kwak Min-Hwan , Ryu Han-Cheol , Kim Young-Tae , Kang Kwang-Yong , Lee Su-Jae , Kim Won-Jeong
Published: September 2003

The effects of anisotropic dielectric properties of ferroelectric Ba1−xSrxTiO3 (BST) films on the characteristics of the interdigital (IDT) capacitors have been studied in microwave regions at room temperature. Ferroelectric BST films with (001), (011), and (111) orientation were epitaxially grown on (001), (011), and (111) MgO substrates, respectively, by the pulsed laser deposition method. The microwave properties of orientation engineered BST films were investigated using interdigital capacitors. The calculated dielectric constant tunability with 40 V dc bias variation and the calculated dielectric quality factor values for IDT capacitors based on (001), (011), and (111) oriented BST films at 9 GHz with no dc bias were about 47%, 55%, 43%, and 12, 14, 21, respectively.
Submicron diamond-lattice photonic crystals produced by two-photon laser nanofabrication
Authors: Kaneko Koshiro , Sun Hong-Bo , Duan Xuan-Ming , Kawata Satoshi
Published: September 2003

Diamond-lattice photonic crystal structures consisting of around 500-nm-diameter 〈111〉 rods and 580-nm-diameter photonic atoms were realized by two-photon photopolymerization. In the course of laser nanofabrication, it was found that the surface quality of elements depended on the crystal geometry, which was then interpreted as voxel floating effect arising from insufficient overlapping degree of voxels. With the solution of this issue, nearly perfect photonic lattices were obtained, from which single-period power rejection of approximately 35% was achieved. This work is an important step toward arbitrarily tailoring the density of photon states of photonic crystals according to end use by engineering cavity or crystalline geometry.
Synthesis and characterization of ZnS bicrystal nanoribbons
Authors: Meng X.-M. , Jiang Y. , Liu J. , Lee C.-S. , Bello I. , Lee S.-T.
Published: September 2003

Here, we report a form of nanostructures bicrystal nanoribbons. Zinc sulfide (ZnS) bicrystal nanoribbons were prepared via simple thermal evaporation of a powder mixture of ZnS and SiO. The product was characterized with transmission electron microscopy (TEM), high-resolution TEM, and electron energy loss spectroscopy. The ZnS bicrystal nanoribbons have widths of 50–500 nm and lengths of several tens of micrometers. Two kinds of growth direction, i.e. [−1−21] and [−1−31], have been found. The growth of the ZnS bicrystal nanoribbons was considered to involve a combination of oxide-assisted and vapor-liquid-solid processes.
Ferroelectricity in Mn-implanted CdTe
Authors: Fu D. J. , Lee J. C. , Choi S. W. , Park C. S. , Panin G. N. , Kang T. W. , Fan X. J.
Published: September 2003

CdTe:Mn was prepared by implantation of CdTe with 200 keV Mn ions with a dose of 5×1016 cm−2, which produced an insulating layer in the surface region. Ferroelectric characterization of the implanted sample revealed a clear hysteresis in its polarization–voltage curves. The remnant polarization of CdTe:Mn amounts to 0.64 μC/cm2 at 400 Hz, and it decreases with increasing temperature in a continuous and diffusive manner. Capacitance measurement demonstrated a maximum capacitance at 140 °C, and fitting of the data with Curie–Weiss law shows the occurrence of a second-order-type phase transition. The ferroelectricity is accounted for by the cation size difference in CdTe:Mn.
Giant dielectric permittivity and electromechanical strain in thin film materials produced by pulsed-laser deposition
Authors: Vrejoiu I. , Pedarnig J. D. , Bäuerle D. , Dinescu M.
Published: September 2003

Thin film materials with a giant dielectric permittivity εr′≈10 000 and an electromechanical strain of Δh/h≈8% are produced by pulsed-laser deposition. Composite targets containing various different oxides such as BaTiO3, BaO2, BaCO3, and TiO2 powder embedded in the polymer polytetrafluoroethylen (PTFE) are employed for laser ablation. The dielectric permittivities of the films show strong relaxation at frequencies above 10 kHz, a pronounced dependence on layer thickness, and a frequency-dependent activation at lower temperatures. Composite targets as well as films produced from BaF2/PTFE targets show only low permittivities with εr′<20 and do not reveal such phenomena.
Co-doped La0.5Sr0.5TiO3−δ: Diluted magnetic oxide system with high Curie temperature
Authors: Zhao Y. G. , Shinde S. R. , Ogale S. B. , Higgins J. , Choudhary R. J. , Kulkarni V. N. , Greene R. L. , Venkatesan T. , Lofland S. E. , Lanci C. , Buban J. P. , Browning N. D. , Das Sarma S. , Millis A. J.
Published: September 2003

Ferromagnetism is observed at and above room temperature in pulsed laser deposited epitaxial films of Co-doped Ti-based oxide perovskite (La0.5Sr0.5TiO3−δ). The system has the characteristics of an intrinsic diluted magnetic semiconductor (metal) at low concentrations (<∼2%), but develops inhomogeneity at higher cobalt concentrations. The films range from being opaque metallic to transparent semiconducting depending on the oxygen pressure during growth and are yet ferromagnetic.
Platinum(100) hillock growth in a Pt/Ti electrode stack for ferroelectric random access memory
Authors: Jung Won Woong , Choi Si Kyung , Kweon Soon Yong , Yeom Seung Jin
Published: September 2003

The Pt hillock in a Pt/Ti electrode stack has been the main concern in ferroelectric random access memory due to the reliability problem. The origin of the hillock formation is the compressive stress, and the main mass transport mechanism for hillock formation is the grain boundary diffusion for thin films with a columnar structure. However, the hillock growth orientation and mechanism have not been reported. In this study, we found that an orientation relationship of Pt(100)hillock//Pt(111)thin film existed between the Pt hillock and the thin film. The Pt hillock was a single crystal having facets with polyatomic steps. From these results, we suggest that the Pt hillock growth mechanism is the layer growth of flat faces, which shapes the hillock into a tetrahedron single crystal.
Room-temperature type-II interband cascade lasers near 4.1 μm
Authors: Yang Rui Q. , Hill Cory J. , Yang Baohua , Liu John K.
Published: September 2003

Operation of type-II interband cascade lasers has been demonstrated in pulsed mode at room temperatures at wavelengths near 4.1 μm. These lasers fabricated with 150 μm wide mesa stripes also operated in cw mode at temperatures up to 145 K. Threshold current densities as low as 9 A/cm2 and output powers exceeding 100 mW/f have been achieved in cw mode at 80 K.
Chemistry and band offsets of HfO2 thin films for gate insulators
Authors: Oshima M. , Toyoda S. , Okumura T. , Okabayashi J. , Kumigashira H. , Ono K. , Niwa M. , Usuda K. , Hirashita N.
Published: September 2003

Interfacial chemistry and band offsets of HfO2 films grown on Si(100) substrates are investigated using high-resolution angle-resolved photoelectron spectroscopy and are correlated with interfacial structures revealed by transmission electron microscope. Hf 4f and O 1s spectra show similar chemical shifts indicating the existence of a double layer structure consisting of a HfO2, upper layer and a SiO2-rich Hf1−xSixO2 lower layer. Two types of valence band offsets are clearly determined by a double subtraction method to be 3.0 and 3.8 eV that can be attributed to ΔEv1 for the upper layer HfO2/Si and ΔEv2 for the lower layer Hf1−xSixO2/Si, respectively.
Promotion of L1 ordered phase transformation by the Ag top layer on FePt thin films
Authors: Zhao Z. L. , Ding J. , Inaba K. , Chen J. S. , Wang J. P.
Published: September 2003

The influence of the deposition of an ultrathin Ag top layer on the structure and magnetic properties of FePt thin films has been investigated. Crystallographic ordering of the L10 face-centered-tetragonal (fct) FePt phase was significantly promoted when a Ag layer was deposited on top of the film. The increased fraction of hard magnetic L10 fct FePt phase led to a dramatic increase of coercivity from 1 to about 6.0 kOe. The δM curves suggested exchange decoupling of magnetic grains. A perpendicular FePt film with a coercivity of 5.0 kOe and remanent squareness of 0.98 was achieved with a CrRu underlayer and the Ag top layer.
Room-temperature GaN vertical-cavity surface-emitting laser operation in an extended cavity scheme
Authors: Park Si-Hyun , Kim Jaehoon , Jeon Heonsu , Sakong Tan , Lee Sung-Nam , Chae Suhee , Park Y. , Jeong Chang-Hyun , Yeom Geun-Young , Cho Yong-Hoon
Published: September 2003

A GaN-based vertical-cavity surface-emitting laser (VCSEL) has been demonstrated in an extended cavity structure. A VCSEL device had a long extended cavity, which consisted of a sapphire substrate as well as a GaN epilayer and had an integrated microlens on one side. High-reflection dielectric mirrors were deposited on both sides of the laser cavity. The laser was optically pumped and operated at room temperature. The VCSEL device lased at a low threshold excitation intensity of 160 kW/cm2. In contrast to a conventional microcavity-VCSEL structure, the VCSEL operated in multiple longitudinal modes with mode spacing consistent with its physical thickness.
Strain effects in and crystal structures of self-assembled InAs/GaAs quantum dots
Authors: Lee H. S. , Lee J. Y. , Kim T. W. , Kim M. D.
Published: September 2003

The strain effects in and the crystal structures of self-assembled InAs/GaAs quantum dots (QDs) were investigated by using transmission electron microscopy (TEM). The in-plane lattice constant of the InAs QDs was larger than that of the GaAs substrate, and the vertical lattice constant of the InAs QDs was smaller than that of the InAs bulk. The variation of the lattice constant for the InAs QD originated from the strain effect. A schematic diagram of a strained InAs QD based on the TEM results, indicative of the strain distribution around the QD, is presented.
Size Effects in ZnO: The Cluster to Quantum Dot Transition
Authors: Wood Annabel , Giersig Michael , Hilgendorff Michael , Vilas-Campos Antonio , Liz-Marzán Luis M. , Mulvaney Paul
Published: September 2003

The use of tetraalkylammonium hydroxides to prepare ZnO colloids with diameters ranging from 1 to 6 nm is described. The position of the first excitonic transition has been measured by UV-vis spectrometry and correlated with the particle size, which has been measured using high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and ultracentrifugation (UC). The exciton transition is first visible at 265–270 nm corresponding to particle diameters around 1 nm; the exciton absorption band then becomes sharper and narrower, while the band red-shifts only slowly. Based on the sizing data from HRTEM, XRD, and UC, it is concluded that the quantum size effect at sizes less than the Bohr radius is significantly less than predicted from the Kayanuma equation. Based on the blue-shift in the trap emission as a function of nanocrystal size, the effective masses of the electron and hole (me, mh) remain constant in particles down to 1 nm in diameter, with a relative value given by me/(me+mh)=0.55 ± 0.04.