The Decline of the Cow: Agricultural and Settlement Change in Early Medieval Ireland

This article considers cows and dairying as the basis a17of value system in early societies, particularly in Ireland. Only in a very few instances is it possible to demonstrate that such systems existed. When it does, it can be shown that cows and dairying were imbedded in the social or religious institutions of these cultures. Cattle had a value and meaning much greater than their economic worth in terms of food, hides, tallow etc. Such a systems, however, does not allow economic development as dairy produce does not easily lend itself to the production, and accumulation, of significant surplus nor is dairy produce particularly suitable for economic expansion based on trade. Its perishable nature militates against both roles. In order to develop political power that is based on economic power and wealth it is necessary to change the emphasis from livestock to cereal production.

Exploitation of inherited weakness in fire-damaged building sandstone: the ‘fatiguing’ of ‘shocked’ stone

The problem of the long-term impact of historical fire on masonry is not clearly understood. Much research focuses on the damage that is caused by fire in isolation, and omits to investigate the subsequent exploitation of weaknesses inherited from fire events. Fire can, for example, cause significant physical, chemical and mineralogical change to sandstone, which may then be exploited by background environmental factors such as salt and freeze–thaw weathering. To explore this experimentally, blocks of Peakmoor Sandstone were subjected to a real fire (as well as lime rendering/removal and frost cycle pre-treatments), and their subsequent response to salt weathering cycles was monitored by weight loss and visual assessment of the pattern of surface damage. Results illustrate that the post-fire deterioration of sandstone is strongly conditioned by fracture networks and soot cover inherited from the fire. The exploitation of fractures can lead to spalling during salt weathering cycles — this takes place as granular dissagregation steadily widens cracks and salts concentrate and crystallise in areas of inherited weakness. Soot cover can have a profound effect on subsequent performance. It reduces surface permeability and can be hydrophobic in character, limiting salt ingress and suppressing decay in the short term. However, as salt crystals concentrate under the soot crust, detachment of this layer can occur, exposing fire-damaged stone beneath. Understanding the subsequent exploitation of stone exposed to fire damage by background environmental factors (for example, salt weathering/ temperature cycling) is key to the post-fire management of stone decay.

Effective monitoring for ractopamine residues in samples of animal origin by SPR biosensor and mass spectrometry

Ractopamine (RCT) is a member of the beta-2-agonist (beta-agonist) family. It is licensed for use as an animal growth promoter in more than 20 countries worldwide, including the United States and Canada, but is either not licensed or prohibited by over 150 others, including those within the European Union. The issue of the use of RCT in livestock bound for human consumption has risen to prominence recently following the decision by The People's Republic of China to ban the import of pork from a number of processing plants after finding traces of RCT in shipments from the U.S.A.

Effects of nateglinide on the secretion of glycated insulin and glucose tolerance in type 2 diabetes

Aims: Glycation of insulin has been demonstrated within pancreatic beta-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes. Methods. Ten patients (5 M/5 F, age 57.8 +/- 1.9 years, HbA(1c), 7.6 +/- 0.5%,, fasting plasma glucose 9.4 +/- 1.2 mmol/l, creatinine 81.6 +/- 4.5 mumol/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min. Results: Plasma glucose and glycated insulin responses were reduced by 9% (P = 0.005) and 38% (P = 0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P = 0.005) and 25% (P = 0.007) by nateglinide. Conclusions: Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the anti hyperglycaemic action of nateglinide. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Necessary conditions for demand revelation in double referenda

This paper demonstrates a set of necessary conditions that should generate unbiased, internally consistent estimates of willingness to pay (WTP) from a double referendum mechanism. These conditions are also sufficient for demand revelation in an experimental laboratory environment. However, the control over the mechanism achieved in the lab may not be transferrable to the field and WTP estimates derived from field surveys may remain biased. (c) 2008 Elsevier Inc. All rights reserved.

Learning design contingent valuation (LDCV): NOAA guidelines, preference learning and coherent arbitrariness

We extend the contingent valuation (CV) method to test three differing conceptions of individuals' preferences as either (i) a-priori well-formed or readily divined and revealed through a single dichotomous choice question (as per the NOAA CV guidelines [K. Arrow, R. Solow, P.R. Portney, E.E. Learner, R. Radner, H. Schuman, Report of the NOAA panel on contingent valuation, Fed. Reg. 58 (1993) 4601-4614]); (ii) learned or 'discovered' through a process of repetition and experience [J.A. List, Does market experience eliminate market anomalies? Q. J. Econ. (2003) 41-72; C.R. Plott, Rational individual behaviour in markets and social choice processes: the discovered preference hypothesis, in: K. Arrow, E. Colombatto, M. Perleman, C. Schmidt (Eds.), Rational Foundations of Economic Behaviour, Macmillan, London, St. Martin's, New York, 1996, pp. 225-250]; (iii) internally coherent but strongly influenced by some initial arbitrary anchor [D. Ariely, G. Loewenstein, D. Prelec, 'Coherent arbitrariness': stable demand curves without stable preferences, Q. J. Econ. 118(l) (2003) 73-105]. Findings reject both the first and last of these conceptions in favour of a model in which preferences converge towards standard expectations through a process of repetition and learning. In doing so, we show that such a 'learning design CV method overturns the 'stylised facts' of bias and anchoring within the double bound dichotomous choice elicitation format. (C) 2007 Elsevier Inc. All rights reserved.

TESTING FOR STATIONARITY IN HETEROGENEOUS PANEL DATA IN THE CASE OF MODEL MISSPECIFICATION

This paper investigates the performance of the tests proposed by Hadri and by Hadri and Larsson for testing for stationarity in heterogeneous panel data under model misspecification. The panel tests are based on the well known KPSS test (cf. Kwiatkowski et al.) which considers two models: stationarity around a deterministic level and stationarity around a deterministic trend. There is no study, as far as we know, on the statistical properties of the test when the wrong model is used. We also consider the case of the simultaneous presence of the two types of models in a panel. We employ two asymptotics: joint asymptotic, T, N -> infinity simultaneously, and T fixed and N allowed to grow indefinitely. We use Monte Carlo experiments to investigate the effects of misspecification in sample sizes usually used in practice. The results indicate that the assumption that T is fixed rather than asymptotic leads to tests that have less size distortions, particularly for relatively small T with large N panels (micro-panels) than the tests derived under the joint asymptotics. We also find that choosing a deterministic trend when a deterministic level is true does not significantly affect the properties of the test. But, choosing a deterministic level when a deterministic trend is true leads to extreme over-rejections. Therefore, when unsure about which model has generated the data, it is suggested to use the model with a trend. We also propose a new statistic for testing for stationarity in mixed panel data where the mixture is known. The performance of this new test is very good for both cases of T asymptotic and T fixed. The statistic for T asymptotic is slightly undersized when T is very small (

Phase I study of GSK461364, a specific and competitive Polo-like Kinase 1 (PLK1) inhibitor in patients with advanced solid malignancies.

Purpose: GSK461364 is an ATP-competitive inhibitor of polo-like kinase 1 (Plk1). A phase I study of two schedules of intravenous GSK461364 was conducted. Experimental Design: GSK461364 was administered in escalating doses to patients with solid malignancies by two schedules, either on days 1, 8, and 15 of 28-day cycles (schedule A) or on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (schedule B). Assessments included pharmacokinetic and pharmacodynamic profiles, as well as marker expression studies in pretreatment tumor biopsies. Results: Forty patients received GSK461364: 23 patients in schedule A and 17 in schedule B. Dose-limiting toxicities (DLT) in schedule A at 300 mg (2 of 7 patients) and 225 mg (1 of 8 patients) cohorts included grade 4 neutropenia and/or grade 3–4 thrombocytopenia. In schedule B, DLTs of grade 4 pulmonary emboli and grade 4 neutropenia occurred at 7 or more days at 100 mg dose level. Venous thrombotic emboli (VTE) and myelosuppression were the most common grade 3–4, drug-related events. Pharmacokinetic data indicated that AUC (area under the curve) and C max (maximum concentration) were proportional across doses, with a half-life of 9 to 13 hours. Pharmacodynamic studies in circulating tumor cells revealed an increase in phosphorylated histone H3 (pHH3) following drug administration. A best response of prolonged stable disease of more than 16 weeks occurred in 6 (15%) patients, including 4 esophageal cancer patients. Those with prolonged stable disease had greater expression of Ki-67, pHH3, and Plk1 in archived tumor biopsies. Conclusions: The final recommended phase II dose for GSK461364 was 225 mg administered intravenously in schedule A. Because of the high incidence (20%) of VTE, for further clinical evaluation, GSK461364 should involve coadministration of prophylactic anticoagulation.

Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata), in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C) residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues). Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.