bluuebunny/crossref_metadata_2025 huggingface dataset:
Choosing Futures: Alva Myrdal and the Construction of Swedish Futures Studies, 1967–1972
Authors: Andersson Jenny
Published: July 2006

This article discusses the Swedish discourse on futures studies in the late 1960s and early 1970s. It focuses on the futures discourse of the group appointed by the Prime Minister, Olof Palme, in 1967 under the chairmanship of Alva Myrdal. The Swedish futures discourse focused on futures studies as a democratic means of reform in defence of the Swedish model and “Swedish” values of solidarity and equality, in opposition to an international futurology dominated by the Cold War and dystopic narratives of global disaster. The article suggests that the creation of Swedish futures studies, culminating in a Swedish institute for futures studies, can be seen as a highpoint of postwar planning and the Swedish belief in the possibility of constructing a particularly Swedish future from a particularly Swedish past.
Disease, diplomacy and international commerce: the origins of international sanitary regulation in the nineteenth century
Authors: Harrison Mark
Published: July 2006

During the early nineteenth century, European nations began to contemplate cooperation in sanitary matters, starting a diplomatic process that culminated in the International Sanitary Conferences and the first laws on the control of infectious disease. This article examines the origins of these conferences and highlights certain features that have been neglected in existing scholarship. It argues that while commercial pressures were the main stimuli to the reform of quarantine, these were insufficient in themselves to explain why most European nations came to see greater cooperation as desirable. It places special emphasis on the diplomatic context and shows that the peace of 1815 produced a climate in which many European nations envisaged a more systematic and liberal sanitary regime.
The Spanish Empire and its legacy: fiscal redistribution and political conflict in colonial and post-colonial Spanish America
Authors: Grafe Regina , Irigoin Maria Alejandra
Published: July 2006

The comparative history of the Americas has been used to identify factors determining longterm economic growth. One approach, new institutional economics (NIE), claims that the colonial origins of respective institutional structures explain North American success and Spanish American failure. Another argues that differences in resources encountered by Europeans fostered divergent levels of equality impacting on institutions and growth. This paper challenges the theoretical premises and historical evidence of both views offering a historicized, statistically and economically validated explanation for the institutional and economic development of Spanish America. First, it revises the structure of the fiscal system challenging the characterization of Spain as an absolutist ruler. Secondly, an analysis of fiscal data at regional levels assesses the performance of the Imperial state. It shows the existence of massive revenue redistribution within the colonies, disputing the notion of a predatory extractive empire based on endowments as the source of original inequality. Finally, we discuss how a contingent event, the imprisonment of the Spanish king in 1808, contributed to the disintegration of a 300-year-old empire. The crisis of legitimacy in the empire turned fiscal interdependence between regions into beggar-thy-neighbour strategies and internecine conflict. We conclude by arguing for a reversal of the causality from weak institutions causing economic failure to fiscal (and economic) failure leading to political instability.
Validität und Reliabilität von Beschwerdenvalidierungstests und -indikatoren
Authors: Blaskewitz Nina , Merten Thomas
Published: July 2006

Zusammenfassung: Beschwerdenvalidierungstests (BVT) dienen zur Überprüfung der Gültigkeit erhaltener Testprofile. Im Rahmen eines Analogdesigns wurden drei BVT (Medical Symptom Validity Test MSVT, Amsterdamer Kurzzeitgedächtnistest AKGT, One-in-Five Test) sowie eine Reihe von Beschwerdenvaliditätsindikatoren anderer Tests auf ihre Güte überprüft. 24 jüngere Erwachsene mit dem Mindestbildungsabschluss Abitur zeigten in der Untersuchung entweder ihre volle Leistung oder waren instruiert, entsprechend einem detaillierten Szenario überzeugend kognitive Störungen vorzutäuschen. Neben den drei BVT wurden folgende neuropsychologische Tests durchgeführt: der Trail Making Test (TMT), der Rey Complex Figure Test and Recognition Trial (RCFT), der Test d2, der Judgment of Line Orientation Test (JLO) und das Zahlennachsprechen des HAWIE-R, woraus auch die Reliable Digit Span (RDS) bestimmt wurde. Für den MSVT, den AKGT und die RDS konnten durch Testwiederholung nach zwei bis drei Tagen bzw. Einsatz einer Äquivalenzform des MSVT Reliabilitätsangaben erhalten werden. Für den AKGT und den MSVT-Durchgang Verzögerte Wiedererkennung ergaben sich zufrieden stellende Reliabilitätskoeffizienten (mit Phi-Koeffizienten von je 0.92), die für die RDS niedriger ausfielen (0.74). Die Ergebnisse zeigen auch eine gute Klassifikationsgüte für die BVT und die RDS, die zwischen 100 % (AKGT) und 79 % (One-in-Five Test) lag. Andere Validitätsindikatoren, die aus TMT, d2 und JLO ermittelt werden, schnitten schlechter ab. Während BVT gegenwärtig die best entwickelte Methodenklasse zur Diagnostik suboptimalen Leistungsverhaltens darstellen, sollte die Güte von Beschwerdenvaliditätsindikatoren, die aus Standardtests abgeleitet werden, deutlich besser überprüft werden, bevor ihr Einsatz in der Einzelfalldiagnostik in Frage kommt.
Employee attachment in the short and long run
Authors: Riketta Michael , Van Dick Rolf , Rousseau Denise M.
Published: July 2006

Abstract. This article discusses the distinction between situated (i. e., temporary and limited) identification and deep-structure (i. e., enduring and multi-faceted) identification with organizations. Research in the social identity tradition suggests that managers can foster employees’ situated identification by emphasizing (a) organizational successes, (b) competition with other firms, (c) employees’ shared features, and (d) personal and organizational distinctiveness. Repeated exposure to these identity reinforcers can turn situated identification into deep-structure identification, especially when employees trust the organization and derive particularistic resources from it (e. g., recognition, information, status). This article concludes with the positive and negative consequences of deep-structure and situated identification for (a) the acceptance of organizational change, (b) reactions to threats to organizational status, and (c) temporary work relationships.
Die Bedeutung kultureller Wertorientierungen für das Commitment gegenüber der Organisation, dem Vorgesetzten, der Arbeitsgruppe und der eigenen Karriere
Authors: Felfe Jörg , Schmook Renate , Six Bernd
Published: July 2006

Zusammenfassung. Vor dem Hintergrund zunehmender Globalisierung von Märkten und Unternehmen stellt sich die Frage, inwieweit kulturelle Unterschiede das Erleben und Verhalten der Mitarbeiter beeinflussen. Diese Studie untersucht auf der individuellen Ebene an einer deutschen Stichprobe mit 349 Beschäftigten den Zusammenhang kultureller Wertorientierungen (Individualismus-Kollektivismus, Machtdistanz und Unsicherheitsvermeidung) mit dem Commitment der Mitarbeiter. Dabei werden unterschiedliche Foci (Organisation, Vorgesetzter, Arbeitsgruppe und die eigene Karriere) mit jeweils drei Komponenten (affektiv, kalkulatorisch und normativ) unterschieden. Mittels konfirmatorischer Faktorenanalysen konnte zunächst die differenzierte Struktur des Commitment-Modells bestätigt werden. Die Ergebnisse zeigen erwartungsgemäße Zusammenhänge zwischen den Kulturorientierungen und Commitment. Kollektivismus korreliert vor allem mit dem Commitment gegenüber der Arbeitsgruppe und der Organisation. Machtdistanz steht in Zusammenhang mit kalkulatorischem Commitment und Unsicherheitsvermeidung korreliert in erster Linie mit kalkulatorischem und normativem Commitment gegenüber der Organisation und der eigenen Karriere. Regressionsanalysen belegen einen eigenständigen Beitrag der Kulturorientierungen zur Vorhersage der einzelnen Facetten von Commitment, wenn relevante Prädiktoren (transformationale Führung, Arbeitsinhalt, Dauer der Betriebszugehörigkeit, Alter) kontrolliert werden. Darüber hinaus moderiert Kollektivismus den Einfluss des Arbeitsinhalts und der transformationalen Führung auf organisationales Commitment. Die Befunde werden in Hinblick auf weiterführende kulturvergleichende Forschungsperspektiven diskutiert.
Characterization of human A2A adenosine receptors with the antagonist radioligand [3H]‐SCH 58261
Authors: Dionisotti Silvio , Ongini Ennio , Zocchi Cristina , Kull Björn , Arslan Giulia , Fredholm Bertil B.
Published: July 2006

We have characterized the binding of the new potent and selective antagonist radioligand [3H]‐5‐amino‐7‐(2‐phenylethyl)‐2‐(2‐furyl)‐pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine, [3H]‐SCH 58261, to human cloned A2A adenosine receptors.

In Chinese hamster ovary (CHO) cells transfected with the human cloned A2A receptor, [3H]‐SCH 58261 specific binding (about 70%) was rapid, saturable, reversible and proportional to protein concentration. The kinetic KD value was 0.75 nM. Saturation experiments showed that [3H]‐SCH 58261 labelled a single class of recognition sites with high affinity (KD=2.3 nM) and limited capacity (apparent Bmax=526 fmol mg−1 protein).

Competition experiments revealed that binding of 0.5 nM [3H]‐SCH 58261 was displaced by adenosine receptor agonists with the following order of potency: 2‐hexynyl‐5′‐N‐ethylcarboxamido‐adenosine (2HE‐NECA)>5′‐N‐ethylcarboxamidoadenosine (NECA)=2‐phenylaminoadenosine (CV 1808)>2‐[4‐(2‐carboxyethyl)‐phenethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680)>R‐N6‐phenylisopropyladenosine (R‐PIA)N6‐cyclohexyladenosine (CHA)>S‐N6‐phenylisopropyladenosine (S‐PIA).

Adenosine receptor antagonists inhibited [3H]‐SCH 58261 binding with the following order: 5‐amino‐9‐chloro‐2‐(2‐furyl)‐[1,2,4]‐triazolo[1,5‐c] quinazoline (CGS 15943)>SCH 58261>xanthine amine congener (XAC)>(E,18%‐Z,82%)7‐methyl‐8‐(3,4‐dimethoxystyryl)‐1,3‐dipropylxanthine (KF 17837S)> 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX)>theophylline.

Affinity values and rank order of potency of both receptor agonists and antagonists were similar to those previously obtained in human platelet and rat striatal membranes, except for CV 1808 which was more potent than CGS 21680. SCH 58261 was a competitive antagonist at inhibiting NECA‐induced adenosine 3′ : 5′‐cyclic monophosphate (cyclic AMP) accumulation in CHO cells transfected with human A2A receptors. Good agreement was found between binding and functional data.

Thus, the new antagonist radioligand is preferable to the receptor agonist radioligand [3H]‐CGS 21680 hitherto used to examine the pharmacology of human cloned A2A adenosine receptors.
Effects of chronic growth hormone treatment in aged rats on the biophysical and pharmacological properties of skeletal muscle chloride channels
Authors: De Luca Annamaria , Pierno Sabata , Cocchi Daniela , Conte Camerino Diana
Published: July 2006

The effects of a 4‐month daily treatment with recombinant human growth hormone (GH) (150 μg kg−1) to aged rats were evaluated on the passive and active membrane electrical properties of extensor digitorum longus (EDL) muscle fibres in vitro by means of a two intracellular microelectrode technique.

Chronic GH treatment completely restored the diameter and the membrane capacitance of aged EDL muscle fibres and significantly lowered the membrane resistance towards the adult value. There was also an increase of the threshold current, a shortening of the latency and an increase of the amplitude of the action potential and a significant amelioration of the membrane firing capability.

The effects were almost fully attributable to a significant 50% increase of resting conductance to chloride ions (GCl), although an observed restoration of potassium conductance and a possible effect on voltage‐activated sodium channels could contribute to the effects.

EDL muscle fibres of untreated aged rats showed a different pharmacological response to 2‐(p‐chlorophenoxy) propionic acid (CPP) enantiomers from that seen in adult rats; the S‐(−) isomer was less potent in blocking GCl and the R‐(+) isomer always increased GCl instead of producing the typical biphasic effect observed in adult fibres (an increase of GCl at 1–10 μM and a decrease at higher concentrations). The 4‐month‐GH‐treated aged rats showed a pharmacological sensitivity to CPP enantiomers similar to that of adults.

The in vitro application of insulin‐like growth factor I (IGF‐I), the peripheral mediator of GH, produced a significant and irreversible increase of GCl of EDL muscle of untreated aged rats, an effect not observed in adults. This effect was completely inhibited by preincubation with 0.5 μM okadaic acid, suggesting that the IGF‐I receptor transduction pathway can act on the phosphorylation state of the chloride channel through a serine‐threonine protein phosphatase.

The results show that the skeletal muscle chloride channel is a target of the impairment of GH/IGF‐I axis occurring in aged subjects. The acute and chronic effects observed on GCl of aged muscle fibres suggest that the GH/IGF‐I stimuli act through a modulation of channel phosphorylation state and through the synthesis of ‘adult’‐like type chloride channels.
Cytochrome P450 1A‐like proteins expressed in the islets of Langerhans and altered pancreatic β‐cell secretory responsiveness
Authors: Clarke Jacqueline , Flatt Peter R. , Barnett Christopher R.
Published: July 2006

The cytochrome P450 (CYP) mixed‐function oxidase system is widely distributed in body tissues and plays a key role in the metabolism of endogenous and exogenous compounds. Little attention has been paid to the expression of the system in the islets of Langerhans. The current study has examined the expression and potential role of the CYP1A family within the islets of Langerhans of control and 3‐methylcholanthrene (3‐MC)‐induced Wistar rats.

CYP1A expression within pancreatic slices and islets from 3‐MC‐induced and control rats demonstrated that CYP1A‐like protein levels were induced by 3‐MC pretreatment (25 mg kg−1 day−1; i.p. for 3 days).

Effects of 3‐MC‐induction on β‐cell secretory responsiveness were investigated by use of rat collagenase‐isolated islets. Insulin release from control islets incubated with 3 mM glucose (basal) was 1.4±0.2 ng/islet h−1 (mean±s.e.mean, n=7). Incubation with 16.7 mM glucose, 25 mM KCl, 100 μM arachidonic acid, or 100 μM carbachol caused a 4.4, 7.0, 4.0 and 4.2 fold, respectively, increase in insulin release (P<0.001). Forskolin (2 μM), or phorbol 12‐myristic 13‐acetate (10 nM) potentiated glucose‐stimulated insulin release 1.2 and 1.6 fold (P<0.01) whereas adenalin (1 μM) caused a 76% inhibition (P<0.01).

Islets from 3‐MC pretreated animals displayed similar responsiveness to all agents tested except arachidonic acid, carbachol and forskolin. Insulin release in response to arachidonic acid and carbachol was enhanced 5.2 and 5.0 fold, respectively, by 3‐MC pretreatment (P<0.001 compared to control islets incubated with 3 mM glucose); the effect of forskolin on insulin output was significantly decreased (20%; P<0.01) compared to control islets.

3‐MC pretreatment did not cause any significant differences in food intake, plasma glucose or total islet insulin content. Incubation of islets with 3‐MC in vitro (1 μM–10 mM) did not affect basal or glucose‐stimulated insulin release.

These data suggest that CYP1A‐like protein expression within the pancreatic islets of Langerhans is inducible and may have a role in the alteration of pancreatic β‐cell secretory responsiveness.
Effect of englitazone on KATP and calcium‐activated non‐selective cation channels in CRI‐G1 insulin‐secreting cells
Authors: Rowe I. C. M. , Lee K. , Khan R. N. , Ashford M. L. J.
Published: July 2006

The effects of englitazone sodium, an antidiabetic agent, on ion channel activity in the CRI‐G1 insulin secreting cell line was examined by use of the patch clamp technique.

Application of englitazone to the outside of CRI‐G1 cells in the whole‐cell recording configuration produced concentration‐dependent inhibition of KATP currents with an IC50 value of 8 μM. The inhibition of the K+ current was not affected by the removal of Mg2+ ions from or the addition of trypsin to the solution bathing the intracellular surface of the cell membrane.

Englitazone also inhibited KATP channel activity in recordings from inside out excised membrane patches. The concentration‐dependence of inhibition was identical to that observed in whole‐cell recordings and was voltage‐independent. Single channel recordings confirmed that neither the absence or presence of Mg2+ ions nor the addition of trypsin at the intracellular surface of the membrane influenced the inhibition of KATP channels by englitazone.

Englitazone also inhibited Ca2+‐activated non‐selective cation (NSCa) channels in inside‐out patches in a concentration‐dependent and voltage‐independent manner with an IC50 value of 10 μM. In comparison, the non‐sulphonylurea KATP channel blocker ciclazindol produced a slight voltage‐dependent inhibition of the NSCa channel at a concentration of 20 μM.

In whole‐cell recordings englitazone, at a relatively high concentration (50 μM) in comparison with that required to block KATP and NSCa channels, inhibited voltage‐activated Ca2+ currents by 33% but did not inhibit voltage‐activated K+ and Na+ currents.

It is concluded that englitazone is a novel blocker of NSCa and KATP channels. The inhibition of KATP channels occurs following procedures that dissociate sulphonylurea receptor coupling to the channel. The equipotent and voltage‐independent inhibition of NSCa and KATP channels by englitazone may indicate a common mechanism of block.
Characterization of nociceptin hyperalgesia and allodynia in conscious mice
Authors: Hara Naoki , Minami Toshiaki , Okuda‐Ashitaka Emiko , Sugimoto Tetsuo , Sakai Masato , Onaka Masahiko , Mori Hidemaro , Imanishi Toshihiro , Shingu Koh , Ito Seiji
Published: July 2006

Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin‐induced allodynia and compared it with the morphine‐induced allodynia and the nociceptin‐evoked hyperalgesia.

Nociceptin‐induced allodynia was evoked by the first stimulus 5 min after i.t. injection, reached a maximum at 10 min, and continued for a 50 min experimental period. Dose‐dependency of the allodynia showed a bell‐shaped pattern from 50 pg to 5 ng kg−1, and the maximum effect was observed at 2.5 ng kg−1.

Morphine‐induced allodynia reached the maximum effect at 15 min and declined progressively until cessation by 40–50 min. The dose‐response curve showed a bell‐shaped pattern, similar to that induced by nociceptin, with a maximum effect at 0.5 mg kg−1, five orders of magnitude higher than that of nociceptin.

The allodynia evoked by nociceptin and morphine were dose‐dependently blocked by glycine, D(−)‐2‐amino‐5‐phosphonovaleric acid (D‐AP5, an N‐methyl‐D‐aspartate (NMDA) receptor antagonist), γ‐D‐glutamylaminomethyl sulphonic acid (GAMS, a non‐NMDA receptor antagonist) and methylene blue (a soluble guanylate cyclase inhibitor), but were not affected by muscimol (a γ‐aminobutyric acidA (GABAA) receptor agonist) and baclofen (a GABAB receptor agonist).

Morphine did not inhibit forskolin‐stimulated cyclicAMP formation in cultured cells expressing the nociceptin receptor.

Nociceptin‐induced hyperalgesia was evoked 10–15 min after i.t. injection. Nociceptin produced a monophasic hyperalgesic action over a wide range of doses from 5 fg to 50 ng kg−1. The nociceptin‐induced hyperalgesia was blocked by glycine only among the agents examined.

None of the pain responses evoked by nociceptin and morphine were blocked by naloxone.

These results demonstrate that, whereas the mechanisms of the nociceptin‐induced allodynia and hyperalgesia are evidently distinct, they involve a common neurochemical event beginning with the disinhibition of the inhibitory glycinergic response. Morphine may induce allodynia through a pathway common to nociceptin, but the nociceptin receptor does not mediate the action of high doses of morphine.
The neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226: effects on vascular responses to exogenous and endogenous NPY in the pig in vivo
Authors: Malmström Rickard E. , Balmér Karin C. , Lundberg Jan M.
Published: July 2006

The antagonistic effects of the neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 on equally prominent vascular responses evoked by sympathetic nerve stimulation and exogenous NPY were compared during different intravenous (i.v.) infusions of the antagonist (0.19–190 nmol kg−1 min−1, for 30 min).

High frequency sympathetic nerve stimulation in reserpine‐treated pigs in vivo evoked non‐adrenergic vasoconstrictor responses in kidney and hind limb, in the latter followed by a long‐lasting phase of decreased blood flow. The vascular response in the kidney and the long‐lasting phase in hind limb resembled the effects of exogenous NPY administered i.v. (kidney) and intraarterially (i.a.) (in the hind limb, which only responded to higher NPY doses).

Plasma levels of BIBP 3226 reached a plateau within 20 min and the inhibitory effects on vascular responses were studied during the last ten minutes of infusion. The elimination of BIBP 3226 from plasma was found to fit a two‐compartment model with an α‐phase of 2.0±0.2 min and a β‐phase of 20.1±0.9 min.

Significant inhibition of presumably Y1 receptor‐mediated vascular responses evoked by both endogenous and exogenous NPY in kidney and hind limb was seen even during low‐dose infusion of BIBP 3226 (1.9 nmol kg−1 min−1), when plasma levels of the antagonist reached 59±8 nM. The maximum inhibitory effects of BIBP 3226 were seen during the highest‐dose infusion (190 nmol kg−1 min−1), when the long‐lasting vasoconstrictor responses in hind limb to sympathetic nerve stimulation and exogenous NPY administration (i.a.) were abolished. Simultaneously, the vascular responses in kidney to exogenous NPY were inhibited by 89% and to sympathetic nerve stimulation by 60%.

It is concluded that BIBP 3226 has a short half‐life in plasma and should preferably be given by i.v. infusions to maintain blockade and avoid non‐specific effects. Furthermore, BIBP 3226 dose‐dependently and with similar potency antagonizes vascular responses to exogenous and endogenous NPY both in the kidney and hind limb of the reserpine‐treated pig in vivo. Thus, inhibition of vascular responses to exogenous NPY may be a good indicator of the dose of this antagonist needed to inhibit sympathetic Y1 receptor‐transmission.
The effect of the neuropeptide substance P on desensitization of ATP receptors of PC12 cells
Authors: Khiroug L. , Giniatullin R. , Talantova M. , Nistri A.
Published: July 2006

Patch clamp recording (whole cell configuration) was employed to investigate the modulatory action of substance P on inward currents elicited by adenosine 5′‐triphosphate (ATP, focally applied via a pressure pipette) from phaechromocytoma (PC12) cells usually held at −70 mV.

Bath‐applied substance P (0.2–20 μM) had no effect on baseline membrane current but reversibly reduced ATP peak currents in a concentration‐dependent fashion. The depressant effect was not associated with a change in the ATP current reversal potential.

Equiamplitude peak responses induced by 50 μM or 5 mM ATP were differentially affected by substance P which preferentially reduced currents evoked by 5 mM ATP. In the presence of substance P a conditioning pulse of ATP evoked a stronger depression to subsequent test pulses of the same agonist.

Combined patch clamping and confocal laser imaging of intracellular Ca2+ ([Ca2+]i) of single PC12 cells showed that substance P (applied by a pressure pipette) per se had no effect on [Ca2+]i or current baseline, although it reduced the inward current and associated [Ca2+]i rise elicited by ATP.

These results are interpreted as due to facilitation by substance P of desensitization of ATP‐gated P2X2 receptors of PC12 cells. It is proposed that the novel modulation by this peptide of ATP responses may serve as a model for further studies aimed at elucidating the action of substance P on purinergic neurotransmission.
Effects of trout bradykinin on the motility of the trout stomach and intestine: evidence for a receptor distinct from mammalian B1 and B2 subtypes
Authors: Jensen Jorgen , Michael Conlon J.
Published: July 2006

Trout bradykinin ([Arg0,Trp5,Leu8]‐bradykinin; trout BK), recently isolated from kallikrein‐treated trout plasma, produced sustained and concentration‐dependent contractions of isolated longitudinal muscle from rainbow trout stomach (pD2=7.01±0.03) and proximal small intestine (pD2=7.37±0.07). The maximum responses were 85±2% (stomach) and 101±35% (intestine) of the corresponding responses to 10−5 M acetylcholine. Strips of circular smooth muscle from trout stomach and intestine did not contract in response to trout BK.

The potency of trout BK on gastric smooth muscle motility was significantly (5 fold; P<0.01) reduced in the presence of the cyclo‐oxygenase inhibitor, indomethacin (10−5 M) and by 4 fold (P<0.05) in the presence of the lipoxygenase inhibitor, MK‐886 (10−6 M), but there was no effect on the maximum response. Potency was also significantly reduced in the presence of 10−6 M methysergide (3 fold; P<0.02) and 10−6 M tetrodotoxin (2 fold, P<0.05) but atropine was without effect.

[Tyr0,Trp5,Leu8]‐BK was a full agonist but was approximately 50 fold less potent (pD2=5.35±0.08) than trout BK, [Arg0,Trp5,Leu8]des‐Arg9‐BK was a partial agonist (pD2=6.80±0.03; 56±7% of the maximum response to trout BK) but [Trp5,Leu8]‐BK, [Trp5,Leu8]‐des‐Arg9‐BK and mammalian BK produced no, or only very weak, contractions of the trout stomach.

The mammalian B1 receptor antagonist, [Leu8]des‐Arg9‐BK was without effect on the response of the trout stomach to trout BK. The potent mammalian B2 receptor antagonist Hoe 140 was a partial agonist (pD2=7.44±0.12; 57±15% of the maximum response to trout BK).

We conclude that the effects of trout BK on the motility of rainbow trout gastric smooth muscle are mediated through interaction with a receptor that has appreciably different ligand‐binding properties than the mammalian B1 and B2 receptor subtypes. An involvement of arachidonic acid metabolites and 5‐hydroxytryptaminergic nerves in the mechanism of action of the peptide is suggested.
A review of the cranial characteristics of the Wild Boar (Susscrofa Linnaeus 1758), with systematic conclusions
Authors: GENOV PETER VASSILEV
Published: July 2006

The Wild Boar Sus scrofa L. is widely distributed in Europe, Asia and North‐West Africa. It has also been introduced into the USA and Argentina. Authors have described 22 subspecies on the basis of cranium shape and size. Differences in taxonomic characters have been evaluated using one‐way ANOVA and multiple comparisons have been performed with the Bonferroni Test. Cranium shape does not allow reliable statistical distinction, and is not valid as a diagnostic tool. Cranium profile‐which only differs for the male specimens, with populations differing at a value of 26.9%, or at the subspecies level 24.4%–cannot be used as a diagnostic tool. The length, width and their proportions of the third upper molar tooth show the following differences between subspecies: 39.1%, 41.0% and 8.3% for males and 36.1%, 41.7% and 16.7% for females, respectively. Only the first two criteria are useful as diagnostic tools. The percentage distance between the palatum durum and the basipterygoideus suture, the length of the third lower molar tooth and proportion between the height of lacrimal bone at the orbit and its lower suture length differ as follows: at the subspecies level 46.7%, 38.5% and 56.4% for the male specimens and 36.1%, 45.8% and 55.6% for the female ones. All of these characters can be used as diagnostic criteria. Taking these taxonomic characters and the four shapes of the lacrimal bone together with the rear margin of palatum durum as a basis, only four subspecies of Wild Boar are recognizable: Sus scrofa scrofa, inhabiting North‐West Africa, Europe and West Asia; Sus scrofa ussuricus, which inhabits North Asia and Japan; Sus scrofa cristatus, which inhabits the Asia Minor peninsula, India and the Far‐East; and Sus scrofa vittatus, which inhabits Indonesia.
Global particle-in-cell simulations of microturbulence with kinetic electrons
Authors: Lewandowski J. L. V. , Rewoldt G. , Ethier S. , Lee W. W. , Lin Z.
Published: July 2006

The effects of nonadiabatic electrons on ion temperature gradient drift instabilities have been studied in global toroidal geometry using the gyrokinetic particle simulation approach. Compared to the nonlinear global simulations based on only the adiabatic response of the electrons, we have found that the cross-field ion heat transport is two to three times larger in the presence of trapped electrons as compared to the purely adiabatic electron case, and that the zonal component of the electrostatic potential has a shorter wavelength. The numerical methods for calculating both the adiabatic and the nonadiabatic responses for the electrons are presented.
Two-dimensional magnetohydrodynamic liner-on-plasma simulations for the compression phase of a magnetized target fusion system based on inverse Z pinch
Authors: Subhash P. V. , Madhavan S. , Chaturvedi S.
Published: July 2006

This article reports, for the first time, two-dimensional magnetohydrodynamic liner-on-plasma simulations for the compression phase of a magnetized target fusion (MTF) system with an inverse Z-pinch target. These simulations evolve the complete liner-plasma system along with the driving pulsed-power source. First, it has been demonstrated that closely coupled liner-on-plasma simulations produce results that are significantly different from loosely coupled simulations that have been reported in the literature. Second, it has been found that an initially stable plasma, satisfying the Kadomtsev criteria, and with a small initial pressure perturbation in the axial direction, remains stable all through the compression phase, even though there are large changes in the pressure and magnetic field levels. Third, a plasma that violates the Kadomtsev criteria, even by a small amount, turns out to be unstable, as predicted by theory. In practical terms, this means that it is preferable to stay well away from the stability limit, even at the cost of some reduction of initial plasma pressure. Fourth, even during the burn phase, when there is a large and rapid increase in plasma pressure due to fusion energy deposition, an initially stable plasma generally tends to remain stable, and even improves its stability margin. This observation shows that the inverse Z pinch is fairly benign as a MTF target, as an initially stable plasma remains stable during both the compression and burn phases. Fifth, certain unusual features are observed in the temperature profile—these depend upon the time scale for implosion. This has implications for plasma-surface interactions at the liner and central conductor.
Wave mode conversion and mode transition in very high radio frequency helicon plasma
Authors: Eom G. S. , Kim Junghee , Choe W.
Published: July 2006

In a very high radio frequency helicon plasma, experimental evidences for a wave mode conversion between the helicon mode and the Trivelpiece-Gould mode (TG mode) are presented. The helicon mode generation was detected when ω<ωce∕2 was satisfied, and the helicon mode was converted to the TG mode at the plasma periphery below 140G. As no more mode conversion to the TG mode occurs above 140G, the plasma was directly heated by the helicon mode and a subsequent abrupt mode transition occurred.
Nitric oxide inhibits exocytosis of cytolytic granules from lymphokine-activated killer cells
Authors: Ferlito Marcella , Irani Kaikobad , Faraday Nauder , Lowenstein Charles J.
Published: July 2006

NO inhibits cytotoxic T lymphocyte killing of target cells, although the precise mechanism is unknown. We hypothesized that NO decreases exocytosis of cytotoxic granules from activated lymphocytes. We now show that NO inhibits lymphokine-activated killer cell killing of K562 target cells. Exogenous and endogenous NO decreases the release of granzyme B, granzyme A, and perforin: all contents of cytotoxic granules. NO inhibits the signal transduction cascade initiated by cross-linking of the T cell receptor that leads to granule exocytosis. In particular, we found that NO decreases the expression of Ras, a critical signaling component within the exocytic pathway. Ectopic expression of Ras prevents NO inhibition of exocytosis. Our data suggest that Ras mediates NO inhibition of lymphocyte cytotoxicity and emphasize that alterations in the cellular redox state may regulate the exocytic signaling pathway.
Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells
Authors: Chute John P. , Muramoto Garrett G. , Whitesides John , Colvin Michael , Safi Rachid , Chao Nelson J. , McDonnell Donald P.
Published: July 2006

Aldehyde dehydrogenase (ALDH) is an enzyme that is expressed in the liver and is required for the conversion of retinol (vitamin A) to retinoic acids. ALDH is also highly enriched in hematopoietic stem cells (HSCs) and is considered a selectable marker of human HSCs, although its contribution to stem cell fate remains unknown. In this study, we demonstrate that ALDH is a key regulator of HSC differentiation. Inhibition of ALDH with diethylaminobenzaldehyde (DEAB) delayed the differentiation of human HSCs that otherwise occurred in response to cytokines. Moreover, short-term culture with DEAB caused a 3.4-fold expansion in the most primitive assayable human cells, the nonobese diabetic/severe combined immunodeficiency mouse repopulating cells, compared with day 0 CD34+CD38−lin−cells. The effects of DEAB on HSC differentiation could be reversed by the coadministration of the retinoic acid receptor agonist,all-trans-retinoic acid, suggesting that the ability of ALDH to generate retinoic acids is important in determining HSC fate. DEAB treatment also caused a decrease in retinoic acid receptor-mediated signaling within human HSCs, suggesting directly that inhibition of ALDH promotes HSC self-renewal via reduction of retinoic acid activity. Modulation of ALDH activity and retinoid signaling is a previously unrecognized and effective strategy to amplify human HSCs.
DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA·TTC repeats in Friedreich's ataxia
Authors: Burnett Ryan , Melander Christian , Puckett James W. , Son Leslie S. , Wells Robert D. , Dervan Peter B. , Gottesfeld Joel M.
Published: July 2006

The DNA abnormality found in 98% of Friedreich's ataxia (FRDA) patients is the unstable hyperexpansion of a GAA·TTC triplet repeat in the first intron of the frataxin gene. Expanded GAA·TTC repeats result in decreased transcription and reduced levels of frataxin protein in affected individuals. β-Alanine-linked pyrrole–imidazole polyamides bind GAA·TTC tracts with high affinity and disrupt the intramolecular DNA·DNA-associated region of the sticky-DNA conformation formed by long GAA·TTC repeats. Fluorescent polyamide-Bodipy conjugates localize in the nucleus of a lymphoid cell line derived from a FRDA patient. The synthetic ligands increase transcription of the frataxin gene in cell culture, resulting in increased levels of frataxin protein. DNA microarray analyses indicate that a limited number of genes are significantly affected in FRDA cells. Polyamides may increase transcription by altering the DNA conformation of genes harboring long GAA·TTC repeats or by chromatin opening.
DOES THE KYOTO PROTOCOL COST TOO MUCH AND CREATE UNBREAKABLE BARRIERS FOR ECONOMIC GROWTH?
Authors: GOLUB ALEXANDER , MARKANDYA ANIL , MARCELLINO DOMINIC
Published: July 2006

We look to the literature on short‐term cost models, long‐term models based on endogenous growth, and long‐term models that assume induced technical change, in order to demonstrate the current understanding of costs, which is the focus of the debate on abating climate change. Using these insights as well as other results—like the role of ancillary benefits and the lack of a relationship between decarbonization and economic growth—our contribution to this debate will be to help policy makers understand how economic analyses are conducted and how they should be used in the subsequent political discussions. (JEL Q52, Q54, Q58)
Dose–response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies
Authors: McQuay Henry J. , Moore R. Andrew
Published: July 2006

Aims

Establishing the dose–response relationship for clinically useful doses of aspirin, ibuprofen and paracetamol has been difficult. Indirect comparison from meta‐analysis is compromised by too little information at some doses.

Methods

A systematic review of randomized, double‐blind trials in acute pain comparing different doses of aspirin, ibuprofen and paracetamol was therefore undertaken.

Results

Fifty trials were found. Numerical superiority of higher over lower dose was found by the original authors in 37/50 trials (74%) and statistical superiority in 11/50 (22%). Twenty‐eight trials had design, quality and data reporting characteristics to allow pooling of common doses; in 3/28 (11%) of the individual trials our calculations showed statistical superiority of higher over lower dose. Pooled comparison of 1000/1200 mg aspirin over 500/600 mg was statistically superior, with a number‐needed‐to‐treat (NNT) for higher over lower dose of 16 (8 to > 100). Pooled comparison of 400 mg ibuprofen over 200 mg was statistically superior, with an NNT for higher over lower dose of 10 (6–23). Pooled comparison of 1000 mg paracetamol over 500 mg was statistically superior, with an NNT for higher over lower dose of 9 (6–20).

Conclusions

Use of trials making direct comparison of two different doses of target drugs revealed the underlying dose–response curve for clinical analgesia.
Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics
Authors: Forgue S. Thomas , Phillips Diane L. , Bedding Alun W. , Payne Christopher D. , Jewell Hayley , Patterson Beverley E. , Wrishko Rebecca E. , Mitchell Malcolm I.
Published: July 2006

Aims

To evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability.

Methods

Six single‐dose (5, 10 or 20 mg orally) clinical pharmacology studies were conducted in the UK, Belgium, Poland and Germany in healthy male and female subjects, elderly subjects and subjects with diabetes mellitus, renal impairment, end‐stage renal failure (ESRF) or hepatic impairment. The gender study also incorporated administration of 10 mg tadalafil daily for 10 days.

Results

Systemic exposure in the elderly was 25% greater than in young subjects (mean AUC ratio 1.25; 90% confidence interval 0.972, 1.61). The AUC was 19% lower in subjects with diabetes mellitus than in healthy age/gender‐matched controls. Pharmacokinetics in female subjects were essentially similar to those in males. Exposure in subjects with mild or moderate renal insufficiency was approximately twice that in healthy subjects. The mean AUC for the major metabolite (total methylcatechol glucuronide) in the presence of ESRF was three times the mean for healthy subjects. Haemodialysis contributed negligibly to elimination of tadalafil or the metabolite. Hepatic impairment had negligible effects on exposure. The most common adverse events in these six studies were headache, back pain and myalgia. A 10‐mg dose was not well tolerated by subjects with moderate renal dysfunction in this study.

Conclusions

No clinically significant effect of gender, age, diabetes mellitus or hepatic impairment on tadalafil pharmacokinetics was observed. Renal insufficiency resulted in increased systemic exposure. Tadalafil was not associated with any serious clinically significant adverse events or study discontinuations due to adverse events.
Public Perceptions of Biotechnology
Authors: Blaine K. , Kamaldeen S. , Powell D.
Published: July 2006

ABSTRACT: Through commercial application, biotechnology may improve health, agriculture, farming practices and the quality of foods. However, along with the array of potential benefits are potential risks and uncertainties surrounding the commercial applications of biotechnology. Public support for a controversial technology such as agricultural biotechnology is crucial for deriving any benefits associated with the technology. Surveys are one tool to gauge public reactions and attitudes over time, and in identifying underlying concerns regarding a technology. This review article is built on the results of a collection of public opinion surveys on some aspects of biotechnology and its applications that have been conducted to date.
Why do we still use stepwise modelling in ecology and behaviour?
Authors: WHITTINGHAM MARK J. , STEPHENS PHILIP A. , BRADBURY RICHARD B. , FRECKLETON ROBERT P.
Published: July 2006

The biases and shortcomings of stepwise multiple regression are well established within the statistical literature. However, an examination of papers published in 2004 by three leading ecological and behavioural journals suggested that the use of this technique remains widespread: of 65 papers in which a multiple regression approach was used, 57% of studies used a stepwise procedure.

The principal drawbacks of stepwise multiple regression include bias in parameter estimation, inconsistencies among model selection algorithms, an inherent (but often overlooked) problem of multiple hypothesis testing, and an inappropriate focus or reliance on a single best model. We discuss each of these issues with examples.

We use a worked example of data on yellowhammer distribution collected over 4 years to highlight the pitfalls of stepwise regression. We show that stepwise regression allows models containing significant predictors to be obtained from each year's data. In spite of the significance of the selected models, they vary substantially between years and suggest patterns that are at odds with those determined by analysing the full, 4‐year data set.

An information theoretic (IT) analysis of the yellowhammer data set illustrates why the varying outcomes of stepwise analyses arise. In particular, the IT approach identifies large numbers of competing models that could describe the data equally well, showing that no one model should be relied upon for inference.
Prenatal Ethanol Exposure Alters the Effects of Gonadectomy on Hypothalamic‐Pituitary‐Adrenal Activity in Male Rats
Authors: Lan N. , Yamashita F. , Halpert A. G. , Ellis L. , Yu W. K. , Viau V. , Weinberg J.
Published: July 2006

Prenatal ethanol exposure has marked effects on development of the hypothalamic‐pituitary‐adrenal (HPA) and ‐gonadal (HPG) axes. In adulthood, ethanol‐treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair‐fed (PF) and ad libitum‐fed control dams. Intact ethanol‐treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress‐induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol‐treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin‐releasing hormone responses in ethanol‐treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol‐treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol‐treated males.
Effects of α‐Melanocyte‐Stimulating Hormone on Magnocellular Oxytocin Neurones and their Activation at Intromission in Male Rats
Authors: Caquineau C. , Leng G. , Guan X. M. M. , Jiang M. , Van der Ploeg L. , Douglas A. J.
Published: July 2006

The peptides α‐melanocyte‐stimulating hormone (α‐MSH) and oxytocin have very similar effects on several behaviours, including male sexual behaviour. Both induce penile erection and enhance copulatory behaviour when given centrally, suggesting that their central actions are not independent. Here, we used intromission as a physiological stimulus to investigate whether some central effects of α‐MSH during male sexual behaviour are mediated by oxytocin neurones. We used the expression of the immediate‐early gene product Fos to investigate oxytocin neurone activation at intromission and after intracerebroventricular (i.c.v.) administration of α‐MSH (1 µg/5 µl) and studied the effects of i.c.v. administration of a MC4 receptor antagonist on Fos expression and on the latency of male rats to exhibit sexual behaviour in the presence of a receptive female. In rats that showed intromission, Fos was expressed in magnocellular oxytocin neurones in both the paraventricular nucleus (PVN) and the supraoptic nucleus (SON), but there was no significant activation of parvocellular oxytocin neurones of the PVN. Similarly, α‐MSH increased Fos expression in magnocellular oxytocin neurones but had little or no effect in parvocellular oxytocin neurones. In male rats that achieved intromission, central injection of a MC4 receptor antagonist significantly attenuated the increase in Fos expression in magnocellular oxytocin neurones in both the PVN and the SON and increased mount and intromission latencies compared to vehicle‐injected controls. Together, the results indicate that magnocellular oxytocin neurones are involved in the central regulation of male sexual behaviour, and that some of the central effects of α‐MSH are likely to be mediated by magnocellular oxytocin neurones.