bluuebunny/crossref_metadata_2025 huggingface dataset:
Concession length and investment timing flexibility
Authors: D'Alpaos Chiara , Dosi Cesare , Moretto Michele
Published: February 2006

When assigning a concession contract, the regulator faces the issue of setting the concession length. Another key issue is whether or not the concessionaire should be allowed to set the timing of new investments. In this paper we investigate the impact of concession length and investment timing flexibility on the “concession value.” It is generally argued that long‐term contracts are privately valuable as they enable a concessionaire to increase its overall discounted returns. Moreover, the real option theory suggests that investment flexibility has an intrinsic value, as it allows concessionaires to avoid costly errors. By combining these two conventional wisdoms one may argue that long‐term contracts, which allow for investment timing flexibility, should always result in higher concession values. Our result suggests that this is not always the case; that is, investment flexibility and long‐term contracts do not necessarily increase the concession value.
Success matters: Recasting the relationship among geophysical, biological, and behavioral scientists to support decision making on major environmental challenges
Authors: Knopman Debra S.
Published: February 2006

Coping with global change, providing clean water for growing populations, and disposing of nuclear waste are some of the most difficult public policy challenges of our time. Unknowns in the physical sciences are one source of the difficulty. Real difficulties in meeting these challenges also arise in the behavioral sciences. A potentially rich vein of transdisciplinary research is to integrate the psychology of decision making, known as “judgment and decision making,” or JDM, with the development of technical information and decision support tools for complex, long‐term environmental problems. Practitioners of JDM conduct research on how individuals and groups respond to uncertainty and ambiguity, hedge against risks, anchor decisions to the status quo, compare relative risks and rewards of alternative strategies, and cope with other classes of decisions. Practitioners use a variety of stimuli, chance devices, hypothetical and real choices involving small stakes, scenarios, and questionnaires to measure (directly and indirectly) preferences under varying conditions. These kinds of experiments can help guide choices about the level of complexity required for different types of decision‐making processes, the value of new data collection efforts, and the ways in which uncertainty in model outcomes can be cast to minimize decision‐making paralysis. They can also provide a scientific basis for interacting with decision makers throughout the model development process, designing better ways of eliciting and combining opinions and of communicating information relevant to public policy issues with the goal of improving the value of the scientific contribution to the social decision.
Hydroecology and river restoration: Ripe for research and synthesis
Authors: Palmer Margaret A. , Bernhardt Emily S.
Published: February 2006

Research at the intersection of hydrology and ecology is central to a future in which human and ecological needs for water are met. We briefly identify several compelling research questions at this intersection, then focus on a critical research area central to hydroecology: river and stream restoration. Challenges in this area include the development of science to evaluate the effectiveness of restoration, particularly the cumulative effects of many small projects; to restore ecosystem processes under highly constrained conditions such as below dams or in urban settings; to push some aquatic ecosystems beyond “restoration” to boost their ability to perform functions of value to society; and to identify feedbacks associated with critical thresholds beyond which restoration is not possible. Meeting these research challenges requires research at the interface of social science and the disciplines of hydrology, geomorphology, ecology, and engineering, but hydroecology will be the central science.
The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model
Authors: Martín Antonio Ramón , Villegas Isabel , Sánchez‐Hidalgo Marina , De La Lastra Catalina Alarcón
Published: February 2006

Neutrophil infiltration, proinflammatory cytokines, eicosanoid generation and oxidative stress have been implicated in colitis. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, including anti‐inflammatory, antioxidant, antitumour and immunomodulatory activities. In a previous report, we documented that resveratrol decreases the degree of inflammation associated with acute experimental colonic inflammation, but its effects on chronic experimental colitis remain undetermined.

The aim of this research was to investigate the effects of resveratrol on the chronic colonic injury caused by intracolonic instillation of trinitrobenzenesulphonic acid (TNBS) in rats. The inflammatory response was assessed by histology and myeloperoxidase activity. Tumour necrosis factor alpha (TNF‐α) production, histological and histochemical analysis of the lesions were also carried out. We determined the production of prostaglandin (PG) E2and D2in colon mucosa, as well as cyclooxygenase (COX)‐1 and ‐2 and nuclear transcription factor NF‐kappa B (NF‐κB) p65 protein expression. Finally, since resveratrol has been found to modulate apoptosis, we intended to elucidate its effects on colonic mucosa under chronic inflammatory conditions.

Resveratrol (10 mg kg−1 day−1) significantly attenuated the damage score and corrected the disturbances in morphology associated to injury. In addition, the degree of neutrophil infiltration and the levels of TNF‐αwere significantly ameliorated. Resveratrol did not modify PGD2levels but returned the decreased PGE2values to basal levels and also reduced COX‐2 and the NF‐κB p65 protein expression. Furthermore, treatment of rats with resveratrol caused a significant increase of TNBS‐induced apoptosis in colonic cells.

In conclusion, resveratrol reduces the damage in chronic experimentally induced colitis, alleviates the oxidative events, returns PGE2production to basal levels and stimulates apoptosis in colonic cells.

British Journal of Pharmacology(2006)147, 873–885. doi:10.1038/sj.bjp.0706469
Aminoglutethimide prevents excitotoxic and ischemic injuries in cortical neurons
Authors: Shirakawa Hisashi , Katsuki Hiroshi , Kume Toshiaki , Kaneko Shuji , Akaike Akinori
Published: February 2006

Aminoglutethimide is a clinically available drug that suppresses steroid biosynthesis by inhibiting enzymes such as cytochromeP450scc and aromatase. Because several members of neurosteroids regulate glutamate receptors, we investigated the effect of aminoglutethimide on cell death induced by overactivation of glutamate receptors in CNS neurons.

Long‐term pretreatment of organotypic cerebrocortical slice cultures with aminoglutethimide (100–1000 μM) for 6 days or over resulted in concentration‐dependent suppression of neuronal cell death induced by NMDA. Aminoglutethimide (1000 μM) also inhibited neurotoxicity of AMPA and kainate, but not of ionomycin or staurosporine.

The protective effect of aminoglutethimide against NMDA cytotoxicity was not mimicked by other steroid synthesis inhibitors including trilostane and exemestane, and was not reversed by concurrent application of steroids such as pregnenolone, estrone, 17β‐estradiol and estriol.

In dissociated rat cerebrocortical cell cultures, long‐term treatment with aminoglutethimide (10–1000 μM) attenuated NMDA receptor‐mediated glutamate cytotoxicity but produced no significant effect on glutamate‐induced increases in intracellular Ca2+.

Brief as well as long‐term pretreatment with aminoglutethimide (30–1000 μM) prevented NMDA receptor‐dependent ischemic neuronal injury in organotypic cerebrocortical slice cultures, which was associated with suppression of glutamate release during the ischemic insult.

These results indicate that aminoglutethimide, irrelevant to its actions on neurosteroid synthesis, protects CNS neurons from excitotoxic and ischemic injuries. Development of aminoglutethimide analogs possessing neuroprotective properties may be of therapeutic value.

British Journal of Pharmacology(2006)147, 729–736. doi:10.1038/sj.bjp.0706636
Mixedβ3‐adrenoceptor agonist andα1‐adrenoceptor antagonist properties of nebivolol in rat thoracic aorta
Authors: Rozec Bertrand , Quang Thuy Tran , Noireaud Jacques , Gauthier Chantal
Published: February 2006

Nebivolol, a selectiveβ‐adrenoceptor (β1‐AR) antagonist, induces vasodilatation by an endothelium‐ and NO‐cGMP‐dependent pathway. However, the mechanisms involved in the vascular effect of nebivolol have not been established. Thus, we evaluated the role ofα1andβ3‐ARs in nebivolol‐induced vasodilatation.

The responses to nebivolol were investigatedin vitroin thoracic aortic rings isolated from male Sprague–Dawley rats.

Nebivolol (0.1–10 μM) significantly shifted the concentration–response curve to phenylephrine, anα1‐AR agonist, to the right in a concentration‐dependent manner (pA2=6.5). Conversely, the concentration–response curve to endothelin 1 (ET1) was unaffected by nebivolol.

In ET1‐precontracted rings, nebivolol induced a concentration‐dependent relaxation, which was unaffected by nadolol (aβ1/β2‐AR antagonist) but was significantly reduced by L‐748,337 (aβ3‐AR antagonist), endothelium removal or pretreatment with L‐NMMA (an NOS inhibitor). Similar results were obtained with aβ3‐AR agonist, SR 58611A.

It was concluded that, in rat aorta, nebivolol‐induced relaxation results from both inhibition ofα1‐ARs and activation ofβ3‐ARs. In addition, we confirmed that the endothelium and the NO pathway are involved in the vascular effect of nebivolol. The identification of these vascular targets of nebivolol indicate that it has therapeutic potential for the treatment of pathological conditions associated with an elevation of sympathetic tone, such as heart failure and hypertension.

British Journal of Pharmacology(2006)147, 699–706. doi:10.1038/sj.bjp.0706648
A novel steroid‐like compound F90927 exerting positive‐inotropic effects in cardiac muscle
Authors: Pignier Christophe , Keller Markus , Vié Bruno , Vacher Bernard , Santelli Maurice , Niggli Ernst , Egger Marcel , Le Grand Bruno
Published: February 2006

Here we report a novel steroid‐like compound F90363, exhibiting positive inotropy in vivo and in vitro in various cardiac muscle preparations.

F90363 is a racemic mixture composed of the stereoisomers (−)‐F90926 and (+)‐F90927. Only F90927 exerted positive inotropy, while F90926 induced a weak negative inotropy, but only at concentrations 103 times higher than F90927 and most likely resulting from an unspecific interaction.

The rapid time course of the action of F90927 suggested a direct interaction with a cellular target rather than a genomic alteration. We could identify the L‐type Ca2+ current ICa(L) as a main target of F90927, while excluding other components of cardiac Ca2+ signalling as potential contributors. In addition, several other signaling pathways known to lead to positive inotropy (e.g. α‐ and β‐adrenergic stimulation, cAMP pathways) could be excluded as targets of F90927.

However, vessel contraction and stiffening of the cardiac muscle at high doses (>30 μM, 0.36 mg kg−1, respectively) prevent the use of F90927 as a candidate for drug development. Since the compound may still find valuable applications in research, the aim of the present study was to identify the cellular target and the mechanism of inotropy of F90927.

British Journal of Pharmacology (2006) 147, 772–782. doi:10.1038/sj.bjp.0706673
Agonist‐specific activation of theβ2‐adrenoceptor/Gs‐protein andβ2‐adrenoceptor/Gi‐protein pathway in adult rat ventricular cardiomyocytes
Authors: Pönicke Klaus , Gröner Ferdinand , Heinroth‐Hoffmann Ingrid , Brodde Otto‐Erich
Published: February 2006

In rat ventricular cardiomyocytesβ2‐adrenoceptors (AR) couple to Gs‐ and Gi‐protein, and evidence has accumulated thatβ2‐AR agonists can differentially activate either Gs‐ or Gs‐ and Gi‐protein.

In this study, in isolated adult rat ventricular cardiomyocytes, we assessed the effects of pertussis toxin (PTX) onβ2‐AR agonist (terbutaline (TER), salbutamol (SAL) and fenoterol (FEN)) evoked inhibition of phenylephrine (PE)‐induced increase in the rate of protein synthesis (assessed as [3H]phenylalanine incorporation) to find out whichβ2‐AR agonist activates selectively Gs‐ or Gs‐ and Gi‐protein.

PE (1 μM) increased the rate of protein synthesis from 100% to 130±2% (n=34). FEN, TER and SAL (1 nM–10 μM) inhibited PE‐induced increase in the rate of protein synthesis concentration‐dependently. FEN inhibited PE effects almost completely (from 132±3 to 101±1%), whereas TER and SAL caused only partial inhibition (from 131±2 to 114±2 and 129±1 to 111±2%, respectively).

Pretreatment of cardiomyocytes with PTX (250 ng ml−1for 16 h at 37°C) did not affect FEN effects, but converted TER‐ and SAL‐evoked partial inhibition into complete inhibition.

Inhibitory effects of the threeβ2‐AR agonists were markedly attenuated byβ1‐AR selective antagonist CGP 20712A (CGP) (300 nM); in contrast,β2‐AR selective antagonist ICI 118,551 (55 nM) inhibited the inhibitory effects of the threeβ2‐AR agonists only in PTX‐pretreated cardiomyocytes, withβ1‐AR blocked by CGP.

We conclude that, in adult rat ventricular cardiomyocytes, FEN activates selectively the Gsprotein‐pathway, while TER and SAL activate the Gs‐ and Gi‐protein pathways. Part of the effects of these threeβ2‐AR agonists appears to be mediated byβ1‐AR.

British Journal of Pharmacology(2006)147, 714–719. doi:10.1038/sj.bjp.0706674
Downregulation of propranolol‐sensitive β‐adrenoceptor signaling after inhibition of nitric oxide synthesis
Authors: Whalen Erin J , Bates James N , Johnson Alan Kim , Lewis Stephen J
Published: February 2006

The β‐adrenoceptor agonist, isoprenaline, elicits vasodilation and tachycardia in anesthetized rats via activation of propranolol‐sensitive β1‐ and β2‐adrenoceptors and also by propranolol‐insensitive β1‐ and β3‐adrenoceptors.

The aim of this study was to determine whether the relative contribution of propranolol‐sensitive and ‐insensitive β‐adrenoceptors to the changes in heart rate (HR) and vascular resistances elicited by isoprenaline is altered after blockade of nitric oxide (NO) synthase, in pentobarbital‐anesthetized rats.

The hemodynamic responses elicited by isoprenaline (0.1 and 0.5 μg kg−1, i.v.) were determined before and after injection of saline or the NO synthase inhibitor, NG‐nitro‐L‐arginine methylester (L‐NAME, 50 μmol kg−1, i.v.), and again after injection of the β1‐ and β2‐adrenoceptor antagonist, propranolol (1 mg kg−1, i.v.). The responses elicited by the above doses of isoprenaline were also determined before and during infusion of the α1‐adrenoceptor agonist, phenylephrine (3 μg kg−1 min−1, i.v.), and again 15–20 min after injection of propranolol (1.0 mg kg−1, i.v.).

Both doses of isoprenaline elicited tachycardia and reductions in vascular resistances. Propranolol eliminated the responses elicited by the lower dose of isoprenaline and substantially diminished the responses elicited by the higher dose of the β1‐, β2‐ and β3‐adrenoceptor agonist. The maximal vasodilator responses elicited by both doses of isoprenaline were not diminished whereas the maximal increases in HR were higher after injection of L‐NAME. The ability of propranolol to diminish the hemodynamic actions of isoprenaline was substantially diminished in L‐NAME‐treated rats, whereas propranolol retained its potency in rats that received an equi‐pressor infusion of the α1‐adrenoceptor agonist, phenylephrine.

The finding that the maximal vasodilator responses elicited by isoprenaline were not diminished by L‐NAME suggests that the vasodilation elicited by this drug was due to direct activation of β‐adrenoceptors on vascular smooth muscle and that the full compliment of isoprenaline‐sensitive receptors was not changed after inhibition of NO synthesis. However, these results suggest that the activities of propranolol‐sensitive β‐adrenoceptors are downregulated, whereas propranolol‐insensitive β‐adrenoceptors are upregulated upon the loss of exposure to endothelial nitrosyl factors.

British Journal of Pharmacology (2006) 147, 755–764. doi:10.1038/sj.bjp.0706675
Species‐dependent smooth muscle contraction to Neuromedin U and determination of the receptor subtypes mediating contraction using NMU1 receptor knockout mice
Authors: Prendergast Clodagh E , Morton Magda F , Figueroa Katherine W , Wu Xiaodong , Shankley Nigel P
Published: February 2006

The peptide ligand neuromedin U (NMU) has been implicated in an array of biological activities, including contraction of uterine, intestinal and urinary bladder smooth muscle. However, many of these responses appear to be species‐specific. This study was undertaken to fully elucidate the range of smooth muscle‐stimulating effects of NMU in rats, mice and guinea‐pigs, and to examine the extent of the species differences. In addition, the NMU1 receptor knockout mouse was used to determine which receptor subtype mediates the contractile responses generated by NMU in the mouse.

A range of isolated organ in vitro bioassays were carried out, which were chosen to re‐confirm previous literature reports (uterine and stomach fundus contraction) and also to explore potentially novel smooth muscle responses to NMU. This investigation uncovered a number of previously unidentified NMU‐mediated responses: contraction of rat lower esophageal sphinster (LES), rat ileum, mouse gallbladder, enhancement of electrically evoked contractions in rat and mouse vas deferens, and a considerable degree of cross‐species differences.

Studies using the NMU1 receptor knockout mice revealed that in the mouse fundus and gallbladder assays the NMU contractile response was mediated entirely through the NMU1 receptor subtype, whereas, in assays of mouse uterus and vas deferens, the response to NMU was unchanged in the NMU1 receptor knockout mouse, suggesting that the NMU response may be mediated through the NMU2 receptor subtype. NMU receptor subtype‐selective antagonists are required to further elucidate the role of the individual receptor subtypes.

British Journal of Pharmacology (2006) 147, 886–896. doi:10.1038/sj.bjp.0706677
Mechanism of hERG K+channel blockade by the fluoroquinolone antibiotic moxifloxacin
Authors: Alexandrou Ari J , Duncan Rona S , Sullivan Anneli , Hancox Jules C , Leishman Derek J , Witchel Harry J , Leaney Joanne L
Published: February 2006

The fluoroquinolone antibiotic moxifloxacin has been associated with the acquired long QT syndrome and is used as a positive control in the evaluation of the QT‐interval prolonging potential of new drugs. In common with other QT‐prolonging agents, moxifloxacin is known to inhibit the hERG potassium K+channel, but at present there is little mechanistic information available on this action. This study was conducted in order to characterise the inhibition of hERG current (IhERG) by moxifloxacin, and to determine the role in drug binding of the S6 aromatic amino‐acid residues Tyr652 and Phe656.

hERG currents were studied using whole‐cell patch clamp (at room temperature and at 35–37°C) in an HEK293 cell line stably expressing hERG channels.

Moxifloxacin reversibly inhibited currents in a dose‐dependent manner. We investigated the effects of different voltage commands to elicit hERG currents on moxifloxacin potency. Using a ‘step‐ramp’ protocol, the IC50was 65 μMat room temperature and 29 μMat 35°C. When a ventricular action potential waveform was used to elicit currents, the IC50was 114 μM.

Block of hERG by moxifloxacin was found to be voltage‐dependent, occurred rapidly and was independent of stimulation frequency.

Mutagenesis of the S6 helix residue Phe656 to Ala failed to eliminate or reduce the moxifloxacin‐mediated block whereas mutation of Tyr652 to Ala reduced moxifloxacin block by ∼66%.

Our data demonstrate that moxifloxacin blocks the hERG channel with a preference for the activated channel state. The Tyr652 but not Phe656 S6 residue is involved in moxifloxacin block of hERG, concordant with an interaction in the channel inner cavity.

British Journal of Pharmacology(2006)147, 905–916. doi:10.1038/sj.bjp.0706678
ROS‐sensitive cytochrome P450 activity maintains endothelial dilatation in ageing but is transitory in dyslipidaemic mice
Authors: Krummen Stéphane , Drouin Annick , Gendron Marie‐Ève , Falck John R , Thorin Eric
Published: February 2006

Risk factors for cardiovascular diseases (CVD) have been proposed to accelerate the vascular endothelial dysfunction that develops during the normal ageing process. The objective of this work was to study the impact of dyslipidaemia (DL) on the dilatory efficacy of the non‐NO/non‐PGI2 endothelium‐derived hyperpolarising factor (EDHF) through maturation and ageing.

We isolated and pressurised (80 mmHg) gracilis arterial segments from 3, 12 and 20‐month‐old (m/o) DL mice expressing the human apolipoprotein B‐100 and wild‐type (WT) C57BL/6 mice. EDHF‐dependent dilatations to acetylcholine (ACh) were measured in the presence of L‐NNA (100 μM, NOS inhibitor) and indomethacin (INDO; 10 μM, COX inhibitor). Data are expressed as mean±s.e.m.

EDHF‐mediated maximal dilatation of arteries isolated from WT mice declined by 44% with ageing, from 86±3% at 3 months to 66±8% at 12 and 48±4% at 20 months of age (P<0.05). This decline was magnified by DL to 73%, characterised by an early increased efficacy at 3 m/o (95±2%, P<0.05) and a worsening of the dysfunction at 20 m/o (26±2%, P<0.05).

17‐Octadecynoic acid (17‐ODYA), a cytochrome P450/epoxygenase inhibitor, reduced by 56% (P<0.05) ACh‐induced EDHF‐dependent dilatation of arteries isolated from 3 m/o DL – but not WT – mice, an effect of 17‐ODYA disappearing in older DL mice. 17‐ODYA, however, reduced (P<0.05) ACh‐induced EDHF‐dependent dilatation in arteries isolated from 12 m/o WT mice by 35% and from 20 m/o WT mice by 31% (P<0.05).

Reactive oxygen species production was increased in arteries isolated from 12 m/o DL mice. The antioxidant N‐acetyl‐L‐cystein (NAC) restored the 17‐ODYA‐sensitive responses in arteries isolated from 12 – but not 20 – m/o DL mice (84±3% from an Emax of 57±8%; P<0.05). NAC did not affect the dilatation of arteries isolated from WT mice.

Our data suggest that the decline in EDHF‐dependent dilatation is hastened by DL despite the early expression of a 17‐ODYA‐sensitive pathway increasing the efficacy of the non‐NO/non‐PGI2 endothelium‐dependent dilatation. Acute free radical production contributes to the endothelial dysfunction in the presence of DL only, by abrogating this latter pathway. This 17‐ODYA‐sensitive pathway, however, appears in 12 m/o WT mice and remains active at 20 m/o.

British Journal of Pharmacology (2006) 147, 897–904. doi:10.1038/sj.bjp.0706679
The proconvulsant effect of sildenafil in mice: role of nitric oxide–cGMP pathway
Authors: Riazi Kiarash , Roshanpour Maryam , Rafiei‐Tabatabaei Neda , Homayoun Houman , Ebrahimi Farzad , Dehpour Ahmad Reza
Published: February 2006

Recent evidence indicates that sildenafil may exert some central effects through enhancement of nitric oxide (NO)‐mediated effects. NO is known to have modulatory effects on seizure threshold, raising the possibility that sildenafil may alter seizure susceptibility through NO‐mediated mechanisms. This study was performed to examine whether sildenafil influences the threshold of clonic and/or generalized tonic seizures through modulation of nitric oxide (NO)–cGMP pathway.

The effect of sildenafil (1–40 mg kg−1) was investigated on clonic seizures induced by intravenous administration of GABA antagonists pentylenetetrazole (PTZ) and bicuculine and on generalized tonic seizures induced by intraperitoneal administration of high dose PTZ in male Swiss mice. The interaction of sildenafil‐induced effects with NO–cGMP pathway was examined using nitric oxide synthase (NOS) inhibitor, N(G)‐nitro‐L‐arginine methyl ester (L‐NAME), NOS substrate L‐arginine, NO donor, sodium nitroprusside (SNP) and guanylyl cyclase inhibitor methylene blue (MB).

Sildenafil induced a dose‐dependent proconvulsant effect in both models of clonic, but not generalized tonic type of seizures. Pretreatment with either MB or L‐NAME inhibited the proconvulsant effect of sildenafil, indicating the mediation of this effect by NO–cGMP pathway. In addition, a subeffective dose of sildenafil induced an additive proconvulsant effect when combined with either L‐arginine or SNP.

Sildenafil induces a proconvulsant effect on clonic seizure threshold that interacts with both exogenously and endogenously released NO and may be linked to activation of NO–cGMP pathway.

British Journal of Pharmacology (2006) 147, 935–943. doi:10.1038/sj.bjp.0706680
Cannabinoid agonists induce relaxation in the bovine ophthalmic artery: evidences for CB1receptors, nitric oxide and potassium channels
Authors: Romano Maria Rosaria , Lograno Marcello D
Published: February 2006

Glaucoma pathophysiology appears to involve vascular deficits, which may contribute to initiation and progression of the disease.

Anandamide, the endogenous cannabinoid ligand, and WIN55212‐2, a synthetic cannabinoid agonist, are able to evoke concentration‐dependent relaxations in bovine ophthalmic artery rings, precontracted with 5‐hydroxytryptamine (5‐HT) (1 μM). Endothelium removal reduces cannabinoid agonist potency and efficacy.

The selective cannabinoid 1 (CB1) receptor antagonists SR141716A (100 nM) and AM251 (100 nM) cause a shift to the right in the concentration–response curves to anandamide and WIN55212‐2 in arterial rings both in the presence and in the absence of endothelium.

In endothelium‐intact arteries, the nitric oxide synthase inhibitor,NG‐monomethyl‐L‐arginine (L‐NMMA, 300 μM), completely blocked the anandamide‐ and WIN55212‐2‐relaxant responses; by contrast, the nitric oxide donorS‐nitroso‐N‐acetylpenicillamine (SNAP, 100 μM) induced an increase in vasorelaxant responses to cannabinoid agonists.

Relaxations to anandamide and WIN55212‐2 were inhibited by iberiotoxin (IbTX, 200 nM), a blocker of large conductance, Ca2+‐activated K+channel (BKCa), and by 4‐aminopyridine (4‐AP; 1 mM), a blocker of delayed rectifier K+channel, whereas the blockade ofKATPchannels by glibenclamide (5 μM) and of small conductance Ca2+‐activated K+channels (SKCa) by apamin (100 nM) did not produce any effects.

These data suggest that anandamide and WIN55212‐2 relax the bovine ophthalmic artery by involving CB1the cannabinoid receptor‐sensitive pathway. In endothelium‐intact arteries, relaxation occurs through activation of nitric oxide synthase cyclic GMP and Ca2+‐activated K+channels. They also cause endothelium‐independent relaxation by involving potassium channel opening.

British Journal of Pharmacology(2006)147, 917–925. doi:10.1038/sj.bjp.0706687
Pharmacological insights obtained from structure–function studies of ionotropic glutamate receptors
Authors: Chen Philip E , Wyllie David J A
Published: February 2006

Ionotropic glutamate receptors mediate the vast majority of fast excitatory synaptic transmission in the CNS. Elucidating the structure of these proteins is central to understanding their overall function and in the last few years a tremendous amount of knowledge has been gained from the crystal structures of the ligand‐binding domains of the receptor protein. These efforts have enabled us to unravel the possible mechanisms of partial agonism, agonist selectivity and desensitization. This review summarizes recent data obtained from structural studies of the binding pockets of the GluR2, GluR5/6, NR1 and NR2A subunits and discusses these studies together with homology modelling and molecular dynamics simulations that have suggested possible binding modes for full and partial agonists as well as antagonists within the binding pocket of various ionotropic glutamate receptor subunits. Comparison of the ligand‐binding pockets suggests that the ligand‐binding mechanisms may be conserved throughout the glutamate receptor family, although agonist selectivity may be explained by a number of features inherent to the AMPA, kainate and NMDA receptor‐binding pockets such as steric occlusion, cavity size and the contribution of water‐bridged interactions.

British Journal of Pharmacology(2006)147, 839–853. doi:10.1038/sj.bjp.0706689
Multifunctional microscope for far-field and tip-enhanced Raman spectroscopy
Authors: Vannier Christophe , Yeo Boon-Siang , Melanson Jeremy , Zenobi Renato
Published: February 2006

The development of a versatile and easy-to-use instrument designed for Raman micro- and nanospectroscopy in the visible range is described in this work. An atomic force microscope, an inverted confocal microscope, and a piezostage are combined to perform an accurate and fast tip-laser alignment and to characterize large areas under the same conditions of illumination across the surface. In addition, a metallized tip is used to locally enhance the electromagnetic field and to probe the sample surface leading to in situ chemical analysis at the nanoscale. Both far-field and tip-enhanced Raman spectroscopies (TERS) have been carried out on dye molecules and on nano-objects with short exposure times. The TERS observation of tip-induced sample deformation on single-walled carbon nanotubes is also presented.
Apparatus for high-resolution microwave spectroscopy in strong magnetic fields
Authors: Huttema W. A. , Morgan B. , Turner P. J. , Hardy W. N. , Zhou Xiaoqing , Bonn D. A. , Liang Ruixing , Broun D. M.
Published: February 2006

We have developed a low-temperature, high-resolution microwave surface-impedance probe that uses cavity perturbation of dielectric resonators and is able to operate in high static magnetic field. This method has sufficient sensitivity to resolve the microwave absorption of submillimeter-sized superconducting samples. The resonators are constructed from high-permittivity single-crystal rutile (TiO2) and have quality factors in excess of 106. Resonators with such high performance have traditionally required the use of superconducting materials, making them incompatible with large magnetic fields and subject to problems associated with aging and power-dependent response. Rutile resonators avoid these problems while retaining comparable sensitivity to surface impedance. Our cylindrical rutile resonators have a hollow bore and are excited in TE01(n−δ) modes, providing homogeneous microwave fields at the center of the resonator where the sample is positioned. Using a sapphire hot-finger technique, measurements can be made at sample temperatures in the range of 1.1–200K, while the probe itself remains immersed in a liquid-helium bath at 4.2K. The novel apparatus described in this article is an extremely robust and versatile system for microwave spectroscopy, integrating several important features into a single system. These include operation at high magnetic fields, multiple measurement frequencies between 2.64 and 14.0GHz in a single resonator, excellent frequency stability, with typical drifts <1Hz∕h, the ability to withdraw the sample from the resonator for background calibration, and a small pot of liquid helium separated from the external bath that provides a sample base temperature of 1.1K. Without modification, this system can be employed for dielectric spectroscopy, electron-spin resonance, and other microwave spectroscopies.
Radiation hardness of a polycrystalline chemical-vapor-deposited diamond detector irradiated with 14 MeV neutrons
Authors: Angelone M. , Pillon M. , Balducci A. , Marinelli M. , Milani E. , Morgada M. E. , Pucella G. , Tucciarone A. , Verona-Rinati G. , Ochiai Kentaro , Nishitani Takeo
Published: February 2006

Chemical-vapor-deposited (CVD) diamond films are considered as neutron detectors for nuclear fusion devices because of their radiation hardness. Data about the radiation hardness of polycrystalline CVD diamond films exposed to 14 MeV neutron are missing in literature so the actual capability of CVD diamond detectors to withstand fusion device conditions must be truly demonstrated. In this work a polycrystalline CVD diamond detector, 101μm thick, was irradiated for the first time with 14 MeV neutrons produced by the Fusion Neutron Source of the Japan Atomic Energy Research Institute with the goal to study its radiation hardness. The 14 MeV neutron fluence was 8×1014n∕cm2. The film performances were studied before and after the 14 MeV neutron irradiation by using 5.5 MeV α from Am241 source, both in the pumped and the “as-grown” state. A comparison with previous measurements performed in more soft neutron spectra (mean neutron energy of 1–2 MeV) is reported pointing out the more damaging effects of the 14 MeV neutrons. It was found that annealing at 500 °C and redeposition of the gold contact followed by a proper pumping procedure will restore more than 70% the initial working conditions of the irradiated detector. An analysis of the neutron field expected in the neutron camera of the International Thermonuclear Reactor fusion tokamak was also performed, showing the capability of CVD diamond detector to withstand the 14 MeV neutron fluence expected in about one year of operation.
Localized spin-wave excitation by the evanescent microwave scanning probe
Authors: Sakran F. , Golosovsky M. , Davidov D. , Monod P.
Published: February 2006

We report a technique for the local contactless spin-wave excitation using the evanescent microwave scanning probe. Our probe is based on a dielectric resonator with the thin slit aperture. It operates at 8.8 GHz, has a spatial resolution of 10–100μm, and may be operated in the parallel and in the perpendicular magnetic field. The measurements can be performed in contact mode or by scanning the sample at constant probe-sample separation. Using 120–150 nm thick Permalloy films on a glass substrate as test samples, we show how our technique can be used for thickness measurements of thin magnetic films and for the mapping of their magnetic properties, such as magnetization and surface anisotropy.
Thermodynamic expressions for the Tolman length
Authors: Blokhuis Edgar M. , Kuipers Joris
Published: February 2006

The Tolman length δ [TolmanJ. Chem. Phys. 17, 333 (1949)] measures the extent by which the surface tension of a small liquid drop deviates from its planar value. Despite increasing theoretical attention, debate continues on even the sign of Tolman’s length for simple liquids. Recent thermodynamic treatments have proposed a relation between the Tolman length and the isothermal compressibility of the liquid at two-phase coexistence, δ≈−κℓσ. Here, we review the derivation of this relation and show how it is related to earlier thermodynamic expressions. Its applicability is discussed in the context of the squared-gradient model for the liquid-vapor interface. It is found that the relation is semiquantitatively correct for this model unless one is too close to the critical point.
Monobridged Si2H4
Authors: McCarthy M. C. , Yu Z. , Sari L. , Schaefer H. F. , Thaddeus P.
Published: February 2006

The rotational spectrum of a new monobridged isomer of Si2H4, denoted here as H2Si(H)SiH, has been detected by Fourier transform microwave spectroscopy of a supersonic molecular beam through the discharge products of silane. On the basis of high-level coupled cluster theory, this isomer is calculated to lie only 7kcal∕mol above disilene (H2SiSiH2), the most stable isomeric arrangement of Si2H4, and to be fairly polar, with a calculated dipole moment of μ=1.14D. The rotational spectrum of H2Si(H)SiH exhibits closely spaced line doubling, characteristic of a molecule undergoing high-frequency inversion. Transition state calculations indicate that inversion probably occurs in two steps: migration of the bridged hydrogen atom to form silylsilylene, H3SiSiH, and then internal rotation of the SiH3 group, followed by the reverse process. The potential energy surface for this type of inversion is quite shallow, with a barrier height of only 2–3kcal∕mol. Searches for the rotational lines of silylsilylene, calculated to be of comparable stability to H2Si(H)SiH but about five times less polar (μ=0.23D), have also been undertaken, so far without success, even though strong lines of H2Si(H)SiH have been detected. The favorable energetics and high polarity of monobridged Si2H4 with respect to either disilene or silylsilylene make it a plausible candidate for radioastronomical detection in sources such as IRC+10216, where comparably large silicon molecules such as SiS, SiC3, and SiC4 have already been discovered.
New design of fiber-optic reflectometer for determining the phase boundary of multicomponent fluid mixtures at high pressures and high temperatures
Authors: Wu Weize , Ke Jie , Poliakoff Martyn
Published: February 2006

A dynamic synthetic method based on an optic fiber sensor has been developed to measure phase boundaries of multicomponent fluid at high temperatures >300°C and pressures >30MPa. The breakthrough has been the design of the equilibrium cell containing the optic fiber, which gives highly reproducible signals for the phase transition. We demonstrate that this method can clearly distinguish between dew points and bubble points in the phase transitions of mixtures. Overall, the method is characterized by speed, simplicity, high pressures, and high temperatures.
Scanning thermal-conductivity microscope
Authors: Sarid Dror , McCarthy Brendan , Grover Ranjan
Published: February 2006

This article describes a novel implementation of an atomic force microscope that can map thermal-conductivity features across a sample with a high spatial resolution. The microscope employs a single-sided, metal-coated cantilever, which acts as a bimetallic strip together with a heating laser whose beam is focused on the cantilever’s free end, on the opposite side of its tip. Subtracting the topography obtained by the unheated and heated cantilevers yields a map of thermal conductivity across the surface of a sample. The article presents (a) the theory of operation of the microscope and (b) the experimental results obtained on a silicon sample with oxide features, showing good agreement between the two.
Direct identification of propargyl radical in combustion flames by vacuum ultraviolet photoionization mass spectrometry
Authors: Zhang T. , Tang X. N. , Lau K.-C. , Ng C. Y. , Nicolas C. , Peterka D. S. , Ahmed M. , Morton Melita L. , Ruscic Branko , Yang R. , Wei L. X. , Huang C. Q. , Yang B. , Wang J. , Sheng L. S. , Zhang Y. W. , Qi F.
Published: February 2006

We have developed an effusive laser photodissociation radical source, aiming for the production of vibrationally relaxed radicals. Employing this radical source, we have measured the vacuum ultraviolet (VUV) photoionization efficiency (PIE) spectrum of the propargyl radical (C3H3) formed by the 193nm excimer laser photodissociation of propargyl chloride in the energy range of 8.5–9.9eV using high-resolution (energy bandwidth=1meV) multibunch synchrotron radiation. The VUV-PIE spectrum of C3H3 thus obtained is found to exhibit pronounced autoionization features, which are tentatively assigned as members of two vibrational progressions of C3H3 in excited autoionizing Rydberg states. The ionization energy (IE=8.674±0.001eV) of C3H3 determined by a small steplike feature resolved at the photoionization onset of the VUV-PIE spectrum is in excellent agreement with the IE value reported in a previous pulsed field ionization-photoelectron study. We have also calculated the Franck-Condon factors (FCFs) for the photoionization transitions C3H3+(X̃;νi,i=1–12)←C3H3(X̃). The comparison between the pattern of FCFs and the autoionization peaks resolved in the VUV-PIE spectrum of C3H3 points to the conclusion that the resonance-enhanced autoionization mechanism is most likely responsible for the observation of pronounced autoionization features. We also present here the VUV-PIE spectra for the mass 39 ions observed in the VUV synchrotron-based photoionization mass spectrometric sampling of several premixed flames. The excellent agreement of the IE value and the pattern of autoionizing features of the VUV-PIE spectra observed in the photodissociation and flames studies has provided an unambiguous identification of the propargyl radical as an important intermediate in the premixed combustion flames. The discrepancy found between the PIE spectra obtained in flames and photodissociation at energies above the IE(C3H3) suggests that the PIE spectra obtained in flames might have contributions from the photoionization of vibrationally excited C3H3 and/or the dissociative photoionization processes involving larger hydrocarbon species formed in flames.
Electron transfer mechanism and the locality of the system-bath interaction: A comparison of local, semilocal, and pure dephasing models
Authors: Weiss Emily A. , Katz Gil , Goldsmith Randall H. , Wasielewski Michael R. , Ratner Mark A. , Kosloff Ronnie , Nitzan Abraham
Published: February 2006

We simulate the effects of two types of dephasing processes, a nonlocal dephasing of system eigenstates and a dephasing of semilocal eigenstates, on the rate and mechanism of electron transfer (eT) through a series of donor-bridge-acceptor systems, D-BN-A, where N is the number of identical bridge units. Our analytical and numerical results show that pure dephasing, defined as the perturbation of system eigenstates through the system-bath interaction, does not disrupt coherent eT because it induces no localization; electron transfer may proceed through superexchange in a system undergoing only pure dephasing. A more physically reasonable description may be obtained via a system-bath interaction that reflects the perturbation of more local electronic structure by local nuclear distortions and dipole interactions. The degree of locality of this interaction is guided by the structure of the system Hamiltonian and by the nature of the measurement performed on the system (i.e., the nature of the environment). We compare our result from this “semilocal” model with an even more local phenomenological dephasing model. We calculate electron transfer rate by obtaining nonequilibrium steady-state solutions for the elements of a reduced density matrix; a semigroup formalism is used to write down the dissipative part of the equation of motion.
Compact variable-temperature magnetic force microscope with optical access and lateral cantilever positioning
Authors: Israel Casey , Hyun Changbae , de Lozanne Alex , Phark Soohyon , Khim Z. G.
Published: February 2006

We describe a compact design for a variable-temperature magnetic force microscope that incorporates a novel mechanical device for the lateral positioning of a piezoresistive cantilever under the guidance of an external optical microscope. The small size of the instrument makes it possible to perform low-temperature experiments by inserting the probe directly into a liquid-helium storage Dewar or into any open or closed liquid-nitrogen container. Besides convenience, this also means that the cycle time for exchanging tips and∕or samples can be as short as 4 h, including warm-up and cooldown. The probe is long enough to reach the middle of an 8 T superconducting magnet. We present the details of this design and show some results.
Magnetization hysteresis loop measurement with a spin-polarized metastable He* beam and an electromagnet of 1.8 kOe
Authors: Kurahashi Mitsunori , Yamauchi Yasushi
Published: February 2006

An experimental apparatus for measuring the magnetization hysteresis loop with a spin-polarized metastable helium (He*) beam, which is an extremely surface-sensitive spin probe, and an electromagnet of 1.8 kOe was developed. The He* beam, spin polarized by optical pumping, was directed to the sample through a hole drilled in the Fe pole pieces of the electromagnet. The sample current difference when reversing the He* spin polarization was measured with a lock-in technique. The hysteresis loop of an Fe∕Cu(100) surface measured at 90 K is presented.
Simple flow through reaction cells for in situ transmission and fluorescence x-ray-absorption spectroscopy of heterogeneous catalysts
Authors: Bare Simon R. , Mickelson George E. , Modica Frank S. , Ringwelski Andrzej Z. , Yang N.
Published: February 2006

We report on the design of both transmission and fluorescence x-ray-absorption spectroscopy cells suitable for in situ characterization of heterogeneous catalysts. The heart of both cells is a quartz tube used to house the catalyst sample. Both cells allow in situ x-ray-absorption fine-structure (XAFS) data to be recorded from −196 to 825 °C using a wide range of gas flows at atmospheric pressure. Excellent temperature control is demonstrated with both designs. XAFS data can be recorded over a wide x-ray energy range (2.1–29 keV). These designs are simple, robust, relatively low cost, and, moreover, are reliable and easy to operate. All of the critical components of the transmission reactor can be purchased commercially, with little machining required. The design of the fluorescence reactor requires access to a skilled glass blower.
Enhanced parametric processes in binary metamaterials
Authors: Gorkunov Maxim V. , Shadrivov Ilya V. , Kivshar Yuri S.
Published: February 2006

We suggest double-resonant (binary) metamaterials composed of two types of magnetic resonant elements, and demonstrate that in the nonlinear regime such metamaterials provide unique possibilities for phase-matched parametric interaction and enhanced second-harmonic generation.
Vacuum arc deposition devices
Authors: Boxman R. L. , Zhitomirsky V. N.
Published: February 2006

The vacuum arc is a high-current, low-voltage electrical discharge which produces a plasma consisting of vaporized and ionized electrode material. In the most common cathodic arc deposition systems, the arc concentrates at minute cathode spots on the cathode surface and the plasma is emitted as a hypersonic jet, with some degree of contamination by molten droplets [known as macroparticles (MPs)] of the cathode material. In vacuum arc deposition systems, the location and motion of the cathode spots are confined to desired surfaces by an applied magnetic field and shields around undesired surfaces. Substrates are mounted on a holder so that they intercept some portion of the plasma jet. The substrate often provides for negative bias to control the energy of depositing ions and heating or cooling to control the substrate temperature. In some systems, a magnetic field is used to guide the plasma around an obstacle which blocks the MPs. These elements are integrated with a deposition chamber, cooling, vacuum gauges and pumps, and power supplies to produce a vacuum arc deposition system.