bluuebunny/crossref_metadata_2025 huggingface dataset:
Debt Stabilizing Fiscal Rules
Authors: MICHEL PHILIPPE , VON THADDEN LEOPOLD , VIDAL JEAN‐PIERRE
Published: September 2010

Unstable government debt dynamics can typically be stabilized around a certain target level of debt by adjustments in various fiscal instruments, like government spending, transfers, or taxes. This paper investigates properties of debt stabilizing rules which link the needed budgetary adjustments to the state of the economy. The paper establishes that the magnitude of the target level of long‐run debt is a key determinant of whether it is possible to find a rule of this type that can be implemented under all available fiscal instruments. Specifically, considering linear feedback rules, the paper demonstrates that there may well exist a critical target level of debt beyond which this is no longer possible. From an applied perspective, this finding is of particular relevance in the context of a monetary union with decentralized fiscal policies. Depending on the target level of debt, there might be a conflict between a common fiscal framework that tracks deficit developments as a function of the state of the economy and the unrestricted choice of fiscal policy instruments at the national level.
A Markov Process for Circular Data
Authors: Kato Shogo
Published: September 2010

We propose a discrete time Markov process which takes values on the unit circle. Some properties of the process, including the limiting behaviour and ergodicity, are investigated. Many computations associated with this process are shown to be greatly simplified if the variables and parameters of the model are represented in terms of complex numbers. A further discussion is given on some submodels, in particular on the stationary process. The proposed model is compared with some existing Markov processes for circular data. Some statistical issues of the model, such as statistical inference, model selection and diagnostic checks, are considered. Finally, an application of the model to wind direction data is provided.
EBION AT THE BARRICADES: MORAL NARRATIVE AND POST‐CHRISTIAN CATHOLIC THEOLOGY
Authors: BARNES MICHEL RENÉ
Published: September 2010

My task in this article is to explore the question of the “place” of moral questions—questions of good and evil—in Christian faith, “faith” here being considered particularly as the content or narrative of belief. The thesis I will argue is that Christianity offers no substantial account or explanation of the origin(s) and nature of evil, that in a fundamental way Christianity is not concerned with offering such accounts, and that when the task of supplying accounts of the origin(s) and nature of evil is made central to the content or narrative of Christian faith that faith is made false: it is misunderstood.
RECONSIDERING BARTH'S REJECTION OF PRZYWARA'S ANALOGIA ENTIS
Authors: JOHNSON KEITH L.
Published: September 2010

Many interpreters argue that Barth's rejection of Erich Przywara's analogia entis is based upon a misinterpretation and that Barth actually incorporated a form of the analogia entis into his mature theology. Through an examination of records from Przywara's visit to Barth's seminar on Thomas Aquinas at the University of Münster in 1929 along with key texts from that period, I argue that Barth did not reject the analogia entis because he misinterpreted it. Rather, he did so on the basis of an accurate account of its meaning and content provided to him personally by Przywara. I also argue that, while Barth's response to the analogia entis did change over the course of his career, he never retracted, either explicitly or implicitly, his rejection of it—nor should he have done so.
Touring the Troubles in West Belfast: Building Peace or Reproducing Conflict?
Authors: Wiedenhoft Murphy Wendy Ann
Published: September 2010

This article examines the development of tourism in West Belfast, Northern Ireland, and explores the extent to which tourism builds peace or reproduces processes of past conflict. Data were collected through semistructured interviews with tour managers and tour guides that include West Belfast in their itineraries and participant observations of tours conducted in West Belfast in the summer of 2007. The findings from this data suggest that while tourism there is reproducing some processes of past conflict, particularly territoriality, it has the potential to build cross‐community relationships.
The American‐Soviet Walks: Large‐Scale Citizen Diplomacy at Glasnost’s Outset
Authors: Brigham Steve
Published: September 2010

Nineteen eighty‐seven was a watershed year in the Soviet Union, as Premier Gorbachev’s glasnost and perestroika initiatives began to change the face of this closed society. On the citizen diplomacy front, the year featured one of the largest‐ever initiatives between American and Soviet citizens, the American–Soviet Walk, the first of numerous walks of that scale to take place in the ensuing years. The five‐week walk not only pushed the limits of this fledgling openness and democratization but also tread well beyond the traditional, safe conventions of small‐scale citizen exchange. This article explores what made these walks unique, from an unexpectedly large peace rally in Novgorod, to an illegal peace demonstration in Red Square, to public meetings with dissidents. It concludes by exploring the deep cultural differences among the citizen representatives from both countries and whether the walks provide a model for future citizen diplomacy when tensions are high between rival countries.
A fine balancing act: freedom and accountability
Authors: Warwick Baroness
Published: September 2010

The recent Funding Options Review identified a minimum additional funding requirement of 900 million per annum for higher education by 2004/05 and also considered more specific needs, such as correcting for past under‐investment in infrastructure. At the same time, it contributed to the debate about the‘key choice’of funding by government or by the‘beneficiaries of higher education.’Government will need to match its aspirations for higher education with adequate funding and the universities will have to be‘even more sensitive and responsive to the needs of students.’
UK universities and the state: a Faustian bargain?
Authors: Dickson Tony
Published: September 2010

The universities are now‘one of the last seminationalised sectors of the British economy,’used by government as an instrument of social policy. This situation represents a‘Faustian bargain’which threatens both the quality and the prosperity of universities. One solution would be privatisation of some universities through public flotation. These universities could then contract with government to take state‐funded students. Two objections are that the scheme would promote elitism and that it would encourage greater inequality between universities, but the relevant question is whether it would offer an improvement on the present regime.
Competitor complaints in anti‐trust enforcement: of Microsoft and mergers
Authors: Gray C. Boyden
Published: September 2010

Competition laws are intended to protect consumers but they can be twisted to serve the interests of competitors. Complaints by competitors can be useful in anti‐trust cases but, in general, antitrust agencies should be‘deeply sceptical’of such complaints which may reflect attempts to seek protection from a more efficient competitor. Both US and EU officials have not been sufficiently sceptical of complaints against Microsoft by its competitors: consumers will pay the price for this error.
Markets in the firm Ken Phillips
Authors: Phillips Ken
Published: September 2010

There is widespread acceptance of the advantages of a market economy but not yet of the next logical step of applying market principles to the internal operations of firms. The use of markets within firms would benefit companies and the economy. It would also require fundamental reappraisal of labour market regulations which imply master‐servant relationships.
ADAM SMITH: REVOLUTIONARY FOR THE THIRD MILLENNIUM?1
Authors: Harris Lord
Published: September 2010

Adam Smith challenged the then prevailing belief in mercantilist control. He presented a picture of an ‘… orderly yet self‐adjusting, dynamic economic system in which rising production, employment, investment and trade were linked spontaneously together by voluntary exchange …’ Present‐day governments and anti‐globalisation protesters could learn a great deal from his writings.
WILLING THE ENDS BUT NOT THE MEANS: A REJOINDER TO THORNTON
Authors: Blundell John
Published: September 2010

Sara Thornton's response to my article was thoughtful and in many ways reassuring. However, police chiefs need to understand the importance of the beat for collecting dispersed information and police forces need the freedom to innovate.
PRIVATE POLICING AND PRIVATE ROADS: A COASIAN APPROACH TO DRUNK‐DRIVING POLICY
Authors: Benson Bruce L.
Published: September 2010

Alcohol‐related traffic accidents are externalities, not because of drinking, but because of relatively free access to public roads. Access limits are Coasian (property‐rights) policies, but more effective limits will arise if road owners are liable for failing to provide safe roads. This can be achieved by privatising roads, thereby creating strong incentives to employ innovative private traffic policing.
POLICING FOR THE PEOPLE
Authors: David Davis
Published: September 2010

Increased spending on law and order over the last decade has not been matched by reductions in crime. The government's claim to have reduced crime does not reflect reality and the public know this. The way to rebuild public confidence and tackle crime is to put more police officers back on the streets. This article argues that in order to do this, four key reforms of the police are needed: a reduction in bureaucracy and central intervention; greater accountability to local communities; more co‐operation between forces; and the modernisation of working practices.
POLICING IN THE UK AND USA: A BRIEF COMPARISON
Authors: Evans Paul
Published: September 2010

The relative advantages and disadvantages of approaches to policing in the UK and USA can be traced back to their different methods of funding and organisation. However, in both cases, the community role is essential for the future of successful policing.
Judicial Exceptions to the Free Provision of Services
Authors: Martín José María Fernández , O'Leary Síofra
Published: September 2010

Abstract: Recent case‐law of the Court of Justice on general interest exceptions to the free provision of services has indicated a flexible approach to general interest exceptions involving moral or ethical issues. In contrast, where the general interest exception is relied on in a case which demonstrates predominantly economic issues, it is subject to strict scrutiny, in particular, with reference to the principle of proportionality. The article analyses the Court's case‐law and tries to deduce the criteria which now govern the Court's position. It also highlights difficulties which this two‐tier approach may excite. The position of the Court of Justice reflects the lack of homogeneous European ethical and moral standards, but it also underlines the predominantly economic character of European integration to date. It is submitted, nevertheless, that divorcing the economic criteria for integration from general ethical considerations will prove an extremely difficult, if not fruitless, task.
The operation and management of agency workers in conditions of vulnerability
Authors: McKay Sonia , Markova Eugenia
Published: September 2010

This article focuses on the operation and management of agency labour by employers and observes that there are strong contradictions between the employers' stated reasons for using agency labour and the employment agencies' perceptions of why such labour is utilised. While discussing agency labour generally, the article also takes account of the position of migrant workers within the agency sector, since agencies have represented a significant route into employment for migrant labour. It draws primarily on 22 in‐depth interviews with employers and employment agencies mainly in the food processing, cleaning and care sectors. The research revealed that while some employers were using agency staff to cover for specific peaks in production, others had used it as an alternative method of dealing with vacancies that otherwise might have resulted in permanent employment.
Novel biologic therapies in development targeting IL‐12/IL‐23
Authors: Van De Kerkhof PCM
Published: September 2010

Recent research has identified the importance of interleukin 12 (IL)‐12 and IL‐23 in the immunopathogenesis of psoriasis. The p40 subunit common to IL‐12 and IL‐23 is an attractive target for selective therapy. Clinical study data are available for two anti‐IL‐12/23 therapies: ustekinumab (CNTO 1275, approved in 2009 for treatment of plaque psoriasis) and ABT‐874. The Phase 3 clinical trials PHOENIX 1 and PHOENIX 2 have shown significant benefit for ustekinumab in moderate‐to‐severe plaque psoriasis, with PASI 75 response rates ranging from 66% at week 12 (after two injections) and rising to 85% at week 24 (after three injections). Withdrawal of treatment led to a gradual return of psoriasis whereas continued therapy every 12 weeks with ustekinumab maintained PASI 75 response. Analysis of safety data demonstrated a safety profile similar to placebo at week 12 and did not reveal any major safety concerns in blocking IL‐12 and IL‐23 for periods as long as 18 months. Phase 2 data indicate that ABT‐874 is also efficacious in the treatment of moderate‐to‐severe plaque psoriasis across a range of dosing strategies.
Trends in the incidence of basal cell carcinoma by histopathological subtype
Authors: Arits AHMM , Schlangen MHJ , Nelemans PJ , Kelleners‐Smeets NWJ
Published: September 2010

Background  As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem.

Objective  In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades.

Methods  We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007.

Results  An annual increase of the number of BCCs of 7% for both genders was shown. The age‐standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100 000 men and from 61.7 to 189.8 per 100 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%.

Conclusion  The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non‐surgically, might reduce the workload in the busy dermatologists practice.
Different phenotypes of segmental vitiligo based on a clinical observational study
Authors: van Geel N , De Lille S , Vandenhaute S , Gauthier Y , Mollet I , Brochez L , Lambert J
Published: September 2010

Background  Segmental vitiligo and generalized vitiligo are in general considered separate entities. However, clinico‐epidemiological data on segmental vitiligo are scarce compared with those of generalized vitiligo.

Objective  To analyse the clinical profile and distribution pattern of lesions in segmental vitiligo patients.

Methods  Segmental vitiligo patients were examined and questioned in a prospective and retrospective setting. The distribution and extent of the lesions were evaluated using clinical photographs.

Results  Different phenotypes of segmental vitiligo were found, including the unilateral segmental type (124 patients; group 1), the bilateral segmental type (three patients; group 2) and the mixed segmental and generalized type (14 patients; group 3). Furthermore, lesions were present with (10%) or without associated halo naevi. The age of onset of segmental vitiligo (median 14 years) was significantly different between the three subgroups (P = 0.028). Extensive involvement of segmental vitiligo lesions on trunk and extremities was significantly (P = 0.031) more observed in patients with a lower age of onset, while the generalized vitiligo lesions in the mixed vitiligo group were mostly very mild. Associated autoimmune diseases were reported in 11%, whereas a positive family history for vitiligo was present in 14.9% of patients. Lesions were not strictly dermatomal nor Blaschkolinear, although a typical recurring pattern could be observed.

Conclusion  Our data provide clinical evidence that segmental vitiligo and generalized vitiligo are parts of the same disease spectrum and that segmental vitiligo could have a polygenetic background as well. Whether different aetiopathological mechanisms underlie the different clinical phenotypes of segmental vitiligo remain to be elucidated.
An interpretation of Babette's Feast as a parable of trauma
Authors: Waldron Sharn
Published: September 2010

Abstract:  In this paper I use the film Babette's Feast as a parable to portray the impasse that often arises out of the experience of complex trauma. The experience of such trauma invokes a crisis of reality. It overflows the boundaries of rational containment. There are no mechanisms with which to apprehend such an event, and consequently it cannot be comprehended; because it cannot be comprehended it cannot be processed. The film Babette's Feast encapsulates the predicament of the individual ensnared in the web of trauma. Although removed from the location and events of her trauma, Babette remains the resident of an austere and colourless environment, her gifts repressed, her brilliance unseen. Healing comes to Babette through her willingness to revisit her true self, a self that has been crushed under the weight of grief and trauma. This revisiting costs her all she has. Yet, it is in this revisiting that she not only frees herself from the austerity of her environment but also engenders purpose and hope within the community who have taken her in. The dissonance of her life is paralleled by the dissonance of the life of the community in which she lives; it is the harmonizing of these dissonances which cannot be spoken that finally gives articulation to the incoherence of Babette's trauma.
The intrinsic innervation of the lung is derived from neural crest cells as shown by optical projection tomography in Wnt1‐Cre;YFP reporter mice
Authors: Freem Lucy J. , Escot Sophie , Tannahill David , Druckenbrod Noah R. , Thapar Nikhil , Burns Alan J.
Published: September 2010

Within the embryonic lung, intrinsic nerve ganglia, which innervate airway smooth muscle, are required for normal lung development and function. We studied the development of neural crest‐derived intrinsic neurons within the embryonic mouse lung by crossing Wnt1‐Cre mice with R26R‐EYFP reporter mice to generate double transgenic mice that express yellow fluorescent protein (YFP) in all neural crest cells (NCCs) and their derivatives. In addition to utilizing conventional immunohistochemistry on frozen lung sections, the complex organization of lung innervation was visualized in three dimensions by combining the genetic labelling of NCCs with optical projection tomography, a novel imaging technique that is particularly useful for the 3D examination of developing organs within embryos. YFP‐positive NCCs migrated into the mouse lung from the oesophagus region at embryonic day 10.5. These cells subsequently accumulated around the bronchi and epithelial tubules of the lung and, as shown by 3D lung reconstructions with optical projection tomography imaging, formed an extensive, branching network in association with the developing airways. YFP‐positive cells also colonized lung maintained in organotypic culture, and responded in a chemoattractive manner to the proto‐oncogene, rearranged during transfection (RET) ligand, glial‐cell‐line‐derived neurotrophic factor (GDNF), suggesting that the RET signalling pathway is involved in neuronal development within the lung. However, when the lungs of Ret−/− and Gfrα1−/− embryos, deficient in the RET receptor and GDNF family receptor α 1 (GFRα1) co‐receptor respectively, were examined, no major differences in the extent of lung innervation were observed. Our findings demonstrate that intrinsic neurons of the mouse lung are derived from NCCs and that, although implicated in the development of these cells, the role of the RET signalling pathway requires further investigation.
First‐trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early‐onset pre‐eclampsia
Authors: Wortelboer EJ , Koster MPH , Cuckle HS , Stoutenbeek Ph , Schielen PCJI , Visser GHA
Published: September 2010

Please cite this paper as: Wortelboer E, Koster M, Cuckle H, Stoutenbeek P, Schielen P, Visser G. First‐trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early‐onset pre‐eclampsia. BJOG 2010;117:1384–1389.

Objective  To investigate the predictive value of maternal serum pregnancy‐associated plasma protein A (PAPP‐A), free β subunit of human chorionic gonadotrophin (fβ‐hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first‐trimester identification of early‐onset pre‐eclampsia.

Design  Nested case–control study.

Setting  Routine first‐trimester screening for trisomy 21 in the Netherlands.

Population  Eighty‐eight women who developed pre‐eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls.

Methods  PP13, PlGF and ADAM12 were measured in stored first‐trimester serum, previously tested for PAPP‐A and fβ‐hCG. All marker levels were expressed in multiples of the gestation‐specific normal median (MoMs). Model predicted detection rates for fixed false‐positive rates were obtained for statistically significant markers alone and in combination.

Main outcome measures  Development of pre‐eclampsia or HELLP syndrome.

Results  PP13 and PlGF were reduced in women with pre‐eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP‐A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fβ‐hCG did not differ between control women and those with pre‐eclampsia. In pre‐eclampsia complicated by a small‐for‐gestational‐age fetus, all markers except fβ‐hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model‐predicted pre‐eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false‐positive rate.

Conclusion  This study demonstrates that PP13 and PlGF in the first‐trimester might be promising markers in risk assessment for early pre‐eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.
Periodontal infection and preterm birth: successful periodontal therapy reduces the risk of preterm birth
Authors: Jeffcoat M , Parry S , Sammel M , Clothier B , Catlin A , Macones G
Published: September 2010

Please cite this paper as: Jeffcoat M, Parry S, Sammel M, Clothier B, Catlin A, Macones G. Periodontal infection and preterm birth: successful periodontal therapy reduces the risk of preterm birth. BJOG 2011;118:250–256.

Objective  This study tested the hypothesis that successful periodontal treatment was associated with a reduction in the incidence of spontaneous preterm birth (PTB).

Design  This was a randomised, controlled, blinded clinical trial.

Setting  Hospital outpatient clinic.

Population  Pregnant women of 6–20 weeks of gestation were eligible.

Methods  Of 322 pregnant women with periodontal disease, 160 were randomly assigned to receive scaling and root planing (SRP, cleaning above and below the gum line), plus oral hygiene instruction, whereas the remaining 162 received only oral hygiene instruction and served as an untreated control group. Subjects received periodontal examinations before and 20 weeks after SRP, and were classified blindly according to the results of treatment into two groups: successful (‘non‐exposure’) and unsuccessful (‘exposure’) treatment. Groups were compared using standard inferential statistics; dichotomous variables were compared using the chi‐square test or logistic regression. Results are presented in terms of odds ratios.

Main outcome measure  The main outcome measure was spontaneous preterm birth before 35 weeks of gestation.

Results  No significant difference was found between the incidence of PTB in the control group (52.4%; n = 162) and the periodontal treatment group (45.6%; n = 160) (P < 0.13, Fisher’s exact test). The incidence of PTB was compared within the periodontal treatment group, considering the success of therapy. A logistic regression analysis showed a strong and significant relationship between successful periodontal treatment and full‐term birth (adjusted odds ratio 6.02; 95% CI 2.57–14.03). Subjects refractory to periodontal treatment were significantly more likely to have PTB.

Conclusions  A beneficial effect on PTB may be dependent on the success of periodontal treatment.
THE CARDIOVASCULAR EFFECTS OF CENTRALLY ADMINISTERED 5‐HYDROXYTRYPTAMINE IN THE CONSCIOUS NORMOTENSIVE AND HYPERTENSIVE RAT
Authors: DALTON D. W.
Published: September 2010

The cardiovascular effects of centrally administered 5‐hydroxytryptamine (5‐HT) have been analysed in conscious normotensive and hypertensive rats.

In conscious normotensive rats, 5‐HT, (1–30 μg) administered intracerebroventricularly (i.c.v.) produced profound and immediate dose‐related decreases in heart rate and small increases in blood pressure. The initial pressor responses were followed by secondary secondary depressor responses at high doses of 5‐HT.

Similar effects were produced by 5‐HT i.c.v. in conscious DOCA‐salt and spontaneously hypertensive rats, although the magnitude of the pressor responses was substantially greater in hypertensive than normotensive rats.

Pretreatment with either N‐methylatropine or atenolol intra‐arterially reduced the 5‐HT‐induced bradycardia in normotensive rats; the reduction was enhanced when both antagonists were given in combination.

The 5‐HT2 antagonist, cyproheptadine (10 μg i.c.v.) increased basal blood pressure and heart rate in normotensive rats. Subsequent administration of 5‐HT i.c.v. produced biphasic effects on heart rate consisting of an initial tachycardia followed by a marked bradycardia.

Methysergide (10 μg i.c.v.) pretreatment did not alter resting heart rate, but attenuated the 5‐HT induced bradycardia. A higher dose of methysergide, (30 μg i.c.v.), decreased resting blood pressure and heart rate.

This study has demonstrated, therefore, that the 5‐HT induced bradycardia is produced by not only a centrally mediated decrease in sympathetic tone, but also an increase in vagal drive to the heart. The bradycardia is antagonised by centrally administered methysergide, but not by cyproheptadine, which suggests that it is probably mediated through a ‘5‐HT1‐like’ receptor mechanism.
NEUROPEPTIDE Y INDUCES AND MODULATES VASOCONSTRICTION IN INTRACRANIAL AND PERIPHERAL VESSELS OF ANIMALS AND MAN
Authors: HANKO J. H. , TÖRNEBRANDT K. , HARDEBO J. E. , KÅHRSTRÖM J. , NOBIN A. , OWMAN CH.
Published: September 2010

Neuropeptide Y (NPY) has recently been reported to coexist with noradrenaline (NA) in central as well as peripheral noradrenergic nerves. NPY‐containing nerve fibres are particularly numerous around blood vessels.

Studies were performed on isolated pial arteries as well as on arteries and veins from several peripheral vascular beds from rabbit, cat and man. NPY induced a varying degree of direct contraction of the vessels with an EAm up to 15 mN. Pial arteries were more sensitive than peripheral arteries to NPY (mean EC50 = 7.6 × 10−9 M). The presence of NPY did not cause any consistent or significant potentiation of the contractile response to NA in any of the vessels tested.

Transmural electrical stimulation of the perivascular nerves (including blockade with tetrodotoxin) was performed mainly with auricular artery from the rabbit. Blocking experiments confirmed that the neurogenic contraction was mediated by noradrenergic‐type fibres. NPY caused a concentration‐related potentiation of the neurally evoked contractile response. The peptide also potentiated the tetrodotoxin‐resistant probably non‐neurogenic contractions obtained during enhanced electrical field stimulation.

It is concluded that NPY interacts with NA during sympathetic nerve activation primarily through a presynaptic effect.
A STUDY ON THE POSTJUNCTIONAL EXCITATORY α‐ADRENORECEPTOR SUBTYPES IN THE MESENTERIC ARTERIAL BED OF THE RAT
Authors: PIPILI EVA
Published: September 2010

The nature of the postsynaptic adrenoreceptor subtypes which mediate vasoconstriction in the mesenteric arterial bed of the rat was investigated using mixed and selective α1, α2and β‐agonists and antagonists.

Phenylephrine (PE) an α1selective agonist and noradrenaline (NA) a mixed α1and α2‐agonist, produced a rise in perfusion pressure (vasoconstriction). The responses to NA remained stable with time whereas responses to PE considerably increased.

UK14304 an α2‐selective agonist at low doses (10−8−10−7moles), caused small, slow contractions in most preparations. Repeated administration of these doses or slightly higher ones, desensitized the tissue to this compound but not to NA or PE. Finally, UK14304 given simultaneously with NA or PE, at doses higher than 5 × 10−7moles, reduced contractions to the latter compounds and this effect was not altered by 10−7M rauwolscine, an α2‐selective antagonist.

Prazosin, an α1‐selective antagonist, as expected, reduced contractions to NA considerably at 10−10−10−8M and abolished contractions to UK14304 at 2 × 10−9M.

Rauwolscine, at 10−8M, potentiated contractions to NA and at 10−6M reduced contractions to both NA and PE (when compared to time controls).

When propranolol (10−6M), a β‐antagonist was included in the perfusion fluid, rauwolscine no longer potentiated responses to NA but reduced them at all concentrations. Under the same conditions rauwolscine affected the responses to PE in a similar direction to that observed in the absence of propranolol.

These results suggest that in the rat mesenteric arterial bed:

rauwolscine exerts an effect additional to α2‐adrenoreceptor antagonism. Modification of this effect by propranolol indicates an interaction between this effect of rauwolscine and the β‐adrenoreceptor.

vasoconstriction in the mesenteric arterial bed of the rat is mainly mediated postsynaptically by α1‐adrenoreceptors although the contribution of an α2‐mediated component cannot be excluded.

UK14304 is an α1‐partial agonist as well as an α2‐agonist.
PHYSIOLOGICAL AND PHARMACOLOGICAL CHARACTERIZATION OF ANINVITROVAGUS NERVE‐TRACHEA PREPARATION FROM GUINEA‐PIG
Authors: WIDMARK E. , WALDECK B.
Published: September 2010

The trachea with the vagus nerves attached was isolated from guinea‐pigs. Contractile responses to nerve stimulation or to drugs were measured as pressure changes in the fluid‐filled lumen.

Electrical stimulation of the vagus nerves caused a prompt increase in the intratracheal pressure with an optimum frequency of stimulation between 20 and 30 Hz. The response to the left vagus was somewhat stronger than the response to the right vagus.

Carbachol caused a maximum pressure increase which was about twice that achieved by bilateral stimulation of the vagus nerves at 20 Hz. In the presence of physostigmine the two sources of stimuli were equally effective.

The excitatory response to stimulation of the vagus nerves was completely inhibited by hexamethonium, atropine and terbutaline. This indicates that the excitatory response is mediated via ganglia with end‐organ responses mediated exclusively by muscarinic receptors and functionally antagonized by stimulation of β2‐adrenoreceptors.

The trachea preparation exhibited an intrinsic tone which was reduced by terbutaline and indomethacin but not by atropine or hexamethonium. It is probable that prostaglandins are involved in the generation of intrinsic tone.

Noradrenaline caused a concentration dependent inhibition of the vagally mediated contractions of the trachea which was antagonized by propranolol and yohimbine. When tracheal tone was induced by carbachol only propranolol was effective thus indicating both pre‐ and postsynaptic effects of noradrenaline.

The present study has shown that the isolated vagus nerve‐trachea is a stable and useful preparation for the evaluation of drugs acting at various levels of the contractile responses of the trachea.
AUTONOMIC INTERPLAY IN VIP‐INDUCED TRACHEAL SMOOTH MUSCLERELAXATION
Authors: VENUGOPALAN C. S. , O'MALLEY NANCY A. , SRIKANDAKUMAR A.
Published: September 2010

VIP‐induced inhibitory responses of the guinea‐pig tracheal pouch, an in vivo preparation designed to demonstrate non‐noradrenergic non‐cholinergic innervation, where determined in chloralose‐urethane anaesthetized animals under control conditions, or pretreated with atropine, propranolol, both atropine and propranolol or atropine‐propranolol with indomethacin.

Of the five groups, the control group showed a significantly greater cumulative dose‐response relaxation to VIP than did the treatment groups.

Among the treatment groups, the propranolol pretreated animals showed significantly greater relaxation than the remaining treatments.

The group that received atropine alone and the combination of atropine and propranolol showed the least relaxation to VIP. The relaxations in these two groups did not differ significantly.

The significantly greater relaxation of the pouch to VIP in the propranolol treated group suggested that the non‐noradrenergic inhibitory mechanism for VIP is dependent upon the existing smooth muscle tone of the pouch.

Pretreatment of the guinea‐pigs with indomethacin did not cause a significant change in the relaxation of the pouch due to VIP suggesting that VIP caused airway smooth muscle relaxation by a mechanism other than that of the release of bronchodilator prostaglandins.
EVIDENCE FOR MEDETOMIDINE AS A SELECTIVE AND POTENT AGONIST α2‐ADRENORECEPTORS
Authors: SAVOLA J.‐M. , RUSKOAHO H. , PUURUNEN J. , SALONEN J. S. , KÄRKI N. T.
Published: September 2010

The activity on α‐adrenoreceptors of medetomidine (±)‐4‐(α,2,3‐trimethylbenzyl)imidazole), an α‐methyl derivative of detomidine, has been characterizedin vivoandin vitrousing detomidine, MPV 207, MPV 295, azepexole, clonidine and xylazine for reference purposes.

Medetomidine (1–100 μg/kg i.v.) was a hypotensive and bradycardic compound in anaesthetized rats. Furthermore, it induced vasopressor (PD501.7 μg/kg) and sympatho‐inhibitory (ID501.6 μg/kg) actions in pithed rats, the effects being antagonized by idazoxan (0.3 mg/kg i.v.) but not by prazosin (0.1 mg/kg i.v.). Medetomidine (30–300 μg/kg i.m.) had an α2‐adrenoreceptor mediated sedative effect on chicks.

Medetomidine was, overall, more potent than detomidine, MPV 207, clonidine, xylazine, MPV 295 or azepexole in central (sedation in the chick) and peripheral (cardiac presynaptic in the pithed rat) actions on α2‐adrenoreceptors. Clonidine had, however, about an equal potency to medetomidine in the vascular smooth muscle of the pithed rat.

Like detomidine and MPV 295, medetomidine had no agonistic activity in the rat aortic ring, but high concentrations antagonized methoxamine‐induced contractions, giving a pA2value of 5.68 for α1‐adrenoreceptor antagonism.

The overall lipophilicity (log P') of medetomidine in the octanol/buffer (pH 7.4, 24–26°C, HPLC technique) was 2.80.

In summary, the experimental data suggest that medetomidine is a lipophilic compound with selective α2‐adrenoreceptor‐stimulating properties and high potency. It may, therefore, prove to be a suitable pharmacologic tool for interventions in α2‐adrenoreceptor mediated effects in the autonomic nervous system.
THE EFFECT OF β‐ADRENORECEPTOR ANTAGONISTS ON THE INHIBITION OF PENDULAR MOVEMENTS OF RABBIT ILEUM PRODUCED BY PERIARTERIAL SYMPATHETIC NERVE STIMULATION AND SOME SYMPATHOMIMETIC AMINES
Authors: NGATIDJAN D. , RAND M. J.
Published: September 2010

The effects of propranolol and of the selective β1and β2‐adrenoreceptor blocking drugs atenolol and ICI 118,551 were determined on the inhibitory responses of isolated segments of rabbit ileum to noradrenaline, isoprenaline and salbutamol and to periarterial sympathetic nerve stimulation.

Responses to isoprenaline (0.04–10.24 μM) and salbutamol (1.4–89.6 μM) were blocked by propranolol in concentrations up to 5.0 and 12.8 μM, respectively. Responses to sympathetic nerve stimulation were reduced but responses to noradrenaline (0.03‐1.92 μM) were unaffected by propranolol in concentrations up to 10.0 and 5.0 μM, respectively.

Atenolol in concentrations up to 30.0 μM blocked responses to isoprenaline (0.04‐2.56 μM) but did not affect responses to noradrenaline, salbutamol or sympathetic nerve stimulation in concentrations up to 3.0,3.0 and 1.0 μM, respectively. However, when responses to noradrenaline and sympathetic nerve stimulation were reduced by phentolamine (1.0 μM), atenolol then produced further reductions.

Responses to isoprenaline (0.04‐2.56 μM) and salbutamol (1.4–89.6 μM) were blocked by ICI 118,551 in concentrations up to 0.5 μM. Responses to sympathetic nerve stimulation were reduced but responses to noradrenaline were unaffected by ICI 118,551 in concentrations up to 0.01 and 0.3 μM, respectively.

Salbutamol (0.1 μM.) increased the inhibitory response to sympathetic nerve stimulation and this effect was blocked by ICI 118,551 (0.01 μM).

It was concluded that blockade of β2‐adrenoreceptors, presumably located on sympathetic nerve terminals, decreases the release of transmitter noradrenaline and that blockade of β1‐adrenoreceptors, presumably located in longitudinal smooth muscle cells, reduces the response to transmitter noradrenaline when α‐adrenoreceptors are also blocked.
The timing of breeding and moult of the Lesser Striped Swallow Hirundo abyssinica
Authors: EARLÉ R. A.
Published: September 2010

The Lesser Striped Swallow seems to have two different breeding populations. The birds south of 10°S breed largely during the spring and summer (July to April) and moult from about April to August. Birds further north breed throughout the year, but mainly during the first seven months of the year. Moult in the birds north of 10°S is from July to February when few birds are breeding. There seem to be two clearly defined moulting populations, with the southern breeding population moulting largely south of 10°S and the east African breeding population moulting largely north of the equator. In both populations moult and breeding seem to be separated in time, at least at the individual level.
The Economics of Hydrogen Fuel Cell Buses*
Authors: COCKROFT COLIN J. , OWEN ANTHONY D.
Published: September 2010

This paper presents the results of a cost‐effectiveness analysis comparing diesel, compressed natural gas and hydrogen fuel cell buses in the Perth bus fleet based on a well‐to‐wheels cost analysis of each technology. Despite its significant environmental benefits in operation, the high initial cost of the prototype hydrogen fuel cell bus means that it cannot compete financially with the fossil fuel technologies. Therefore, the study was undertaken assuming that the buses, including fuel cells, are produced under conditions of economies of scale and that a fully developed fuel infrastructure for the provision of hydrogen exists.
Sclerotic plates or circumorbital bones in early jawed fishes?
Authors: BURROW CAROLE J. , NEWMAN MICHAEL J. , DAVIDSON ROBERT G. , DEN BLAAUWEN JAN L.
Published: September 2010

Abstract:  Circumorbital dermal bones are found in most groups of early vertebrates that have dermal bony plates on the head. Taxonomic distribution of dermal sclerotic plates on the eye itself is less clear, partly because the eyeball is rarely preserved and sometimes because sclerotic bones have been misinterpreted as circumorbital bones. Based on the examination of climatiid Climatius plus mesacanthid, cheiracanthid and acanthodid acanthodiform acanthodians, we conclude that most, if not all, acanthodiforms and climatiids had sclerotic rings. Presence and number of these elements should be included as a character in phylogenetic analyses of early jawed vertebrates.
Protocatechuic acid inhibits cancer cell metastasis involving the down‐regulation of Ras/Akt/NF‐κB pathway and MMP‐2 production by targeting RhoB activation
Authors: Lin Hui‐Hsuan , Chen Jing‐Hsien , Chou Fen‐Pi , Wang Chau‐Jong
Published: September 2010

BACKGROUND AND PURPOSE Protocatechuic acid (PCA) is plentiful in edible fruits and vegetables and is thus one anti‐oxidative component of normal human diets. However, the molecular mechanisms involved in the chemopreventive activity of PCA are poorly understood. Here, we investigated the mechanism(s) underlying the anti‐metastatic potential of PCA.

EXPERIMENTAL APPROACH We used AGS cells in a wound healing model and Boyden chamber assays in vitro and injection of B16/F10 melanoma cells in mice (metastasis model in vivo) to analyse the effect of PCA on cancer cell invasion and metastasis. The activities and expression of molecular proteins were measured by zymographic assay, real‐time RT‐PCR and Western blotting.

KEY RESULTS PCA inhibited cell migration and invasion at non‐cytotoxic concentrations. Decreased expression of matrix metalloproteinase (MMP)‐2 and a coincident increase in tissue inhibitor of MMP followed treatment with PCA. The PCA‐inhibited MMP‐2 activity and expression was accompanied by inactivation of NF‐κB. All these effects of PCA could be mediated via the RhoB/ protein kinase Cε (PKCε) and Ras/Akt cascade pathways, as demonstrated by inhibition of PKCε and transfection of PKCε siRNA and ras overexpression vector. Finally, PCA inhibited metastasis of B16/F10 melanoma cells to the liver in mice.

CONCLUSION AND IMPLICATIONS Our data imply that PCA down‐regulated the Ras/Akt/NF‐κB pathway by targeting RhoB activation, which in turn led to a reduction of MMP‐mediated cellular events in cancer cells and provides a new mechanism for the anti‐cancer activity of PCA.
Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat
Authors: Able SL , Fish RL , Bye H , Booth L , Logan YR , Nathaniel C , Hayter P , Katugampola SD
Published: September 2010

BACKGROUND AND PURPOSE The P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described.

EXPERIMENTAL APPROACH Autoradiography studies using the P2X7 antagonist radioligand [3H]‐A‐804598 were carried out in rat brain and spinal cord. Subsequent in vitro binding and ex vivo occupancy assays were performed using rat cortex homogenate.

KEY RESULTS P2X7 expression was shown to be widespread throughout the rat brain, and in the grey matter of the spinal cord. In binding assays in rat cortex homogenate, ∼60% specific binding was achieved at equilibrium. In kinetic binding assays, kon and koff values of 0.0021·min−1·nM−1 and 0.0070·min−1 were determined, and the Kd derived from kinetic measurements was consistent with that derived from saturation analysis. Novel P2X7 antagonists inhibited the binding of [3H]‐A‐804598 to rat cortex P2X7 receptors with Ki values of <40 nM. In an ex vivo occupancy assay, a P2X7 antagonist dosed orally to rats caused a concentration‐dependent inhibition of the specific binding of [3H]‐A‐804598 to rat cortex.

CONCLUSIONS AND IMPLICATIONS The present study describes the development of an assay that allows localization of P2X7 receptors, the measurement of the binding affinity of P2X7 receptor antagonists in native tissue, and provides a means of determining central P2X7 receptor occupancy. These assays could form an important part of a P2X7 drug discovery programme.
Effects of systemic inhibition of Rho kinase on blood pressure and renal haemodynamics in diabetic rats
Authors: Komers R , Oyama TT , Beard DR , Anderson S
Published: September 2010

BACKGROUND AND PURPOSE The RhoA/Rho associated kinases (ROCK) pathway has been implicated in the pathophysiology of diabetic nephropathy (DN). Early stages of diabetes are associated with renal haemodynamic changes, contributing to later development of DN. However, the role of RhoA/ROCK, known regulators of vascular tone, in this process has not been studied.

EXPERIMENTAL APPROACH Blood pressure (BP), glomerular filtration (GFR), effective renal plasma flow and filtration fraction (FF) in response to the ROCK inhibitors Y27632 (0.1 and 0.5 mg·kg−1) and fasudil (0.3 and 1.5 mg·kg−1) were examined in streptozotocin‐diabetic rats and non‐diabetic controls.

KEY RESULTS Diabetic rats demonstrated baseline increases in GFR and FF. In contrast to similar decreases in BP in diabetic and control rats, renal vasodilator effects and a decrease in FF, following ROCK inhibition were observed only in diabetic rats. The vasodilator effects of Y27632 and a further decrease in FF, were also detected in diabetic rats pretreated with the angiotensin antagonist losartan. The effects of ROCK inhibitors in diabetic rats were modulated by prior protein kinase C (PKC)β inhibition with ruboxistaurin, which abolished their effects on FF. Consistent with the renal vasodilator effects, the ROCK inhibitors reduced phosphorylation of myosin light chain in diabetic kidneys.

CONCLUSIONS AND IMPLICATIONS The results indicate greater dependence of renal haemodynamics on RhoA/ROCK and beneficial haemodynamic effects of ROCK inhibitors in diabetes, which were additive to the effects of losartan. In this process, the RhoA/ROCK pathway operated downstream of or interacted with, PKCβ in some segments of the renal vascular tree.
The Breakthrough of Another West European Populist Radical Right Party? The Case of the True Finns
Authors: Arter David
Published: September 2010

The True Finn Party (PS), which gained virtually 10 per cent of the national vote at the 2009 European Parliament election, lacks a place in the comparative party literature and also defies ready classification. It has been perceived by its supporters as the most left-wing of the non-socialist parties; by Finnish media commentators as a case of right-wing populism; and by researchers as a distinctive centred-based populist party when viewed in a wider European perspective. Based on a careful study of its programmatic output since its inception in 1995, this article seeks to characterize the PS by reference to its core ideological features. It argues that it is in fact a populist radical right party – with national identity or Finnishness as its pivotal concept – albeit without the xenophobic extremism of such continental counterparts as the Danish People's Party or Austrian Freedom Party.
Survivorship and growth in the larvae of Luehdorfia japonica feeding on old leaves of Asarum megacalyx
Authors: HATADA Aya , MATSUMOTO Kazuma
Published: September 2010

Although the papilionid butterfly Luehdorfia japonica, usually lays eggs on new leaves of the host plant (Asarum sp.; Aristolochiaceae), eggs of the butterfly were frequently found on old leaves of Asarum megacalyx in Suyama, Tokamachi, Niigata prefecture. Larvae hatched on new leaves and those hatched on old leaves did not show significant differences in their survival rate in the field. In laboratory breeding, about 90% of larvae that were fed old leaves survived and developed normally to the pupal stage. Their growth rate, however, was slightly lower than those that were fed new leaves. No nutritional differences were found between the old and new leaves. The reason why oviposition on the old leaves was so frequent and why larvae that hatched on old leaves could survive in the study area is discussed.