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.

Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling

We performed comprehensive genome-wide gene expression profiling (GEP) of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed, paraffin-embedded tissue (n = 9) and NK cell lines (n = 5) in comparison with normal NK cells, with the objective of understanding the oncogenic pathways involved in the pathogenesis of NKTL and to identify potential therapeutic targets. Pathway and network analysis of genes differentially expressed between NKTL and normal NK cells revealed significant enrichment for cell cycle-related genes and pathways, such as PLK1, CDK1, and Aurora-A. Furthermore, our results demonstrated a pro-proliferative and anti-apoptotic phenotype in NKTL characterized by activation of Myc and nuclear factor kappa B (NF-kappa B), and deregulation of p53. In corroboration with GEP findings, a significant percentage of NKTLs (n = 33) overexpressed c-Myc (45.4%), p53 (87.9%), and NF-kappa B p50 (67.7%) on immunohistochemistry using a tissue microarray containing 33 NKTL samples. Notably, overexpression of survivin was observed in 97% of cases. Based on our findings, we propose a model of NKTL pathogenesis where deregulation of p53 together with activation of Myc and NF-kappa B, possibly driven by EBV LMP-1, results in the cumulative up-regulation of survivin. Down-regulation of survivin with Terameprocol (EM-1421, a survivin inhibitor) results in reduced cell viability and increased apoptosis in tumour cells, suggesting that targeting survivin may be a potential novel therapeutic strategy in NKTL. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Comprehensive Inhibitor Profiling Of The Proteus Mirabilis Metalloprotease Virulence Factor Zapa (Mirabilysin)

In this study we report for the first time the comprehensive inhibitor profiling of the Proteus mirabilis metalloprotease virulence factor, ZapA (mirabilysin) using a 160 compound focused library of N-alpha mercaptoamide dipeptides, in order to map the S1´ and S2´ binding site preferences of this important enzyme. This study has revealed a preference for the aromatic residues tyrosine and tryptophan in P1´ and aliphatic residues in P2´. From this library, six compounds were identified which exhibited sub- to low micromolar Ki values. The most potent inactivator, SH-CO2-Y-V-NH2 was capable of preventing ZapA-mediated hydrolysis of heat denatured IgA, indicating these inhibitors may be capable of protecting host proteins against ZapA during colonisation and infection.

The ontogenesis of lateralized behavior in the domestic cat, Felis silvestris catus

For the first time, the development of paw preferences in the domestic cat, Felis silvestris catus, is explored. Twelve cats were tested at ages 12 weeks, 6 months, and 1 year on a challenge requiring them to use one of their paws to retrieve food. To control for repeated testing of the same cats at different ages, the subjects' paw preferences were compared with those of cats tested just once, at 6 months (n = 11) or 1 year (n = 14) of age. Analysis revealed a significant effect of age on the distribution of cats' paw preferences. Cats were significantly more likely to be ambilateral than paw preferent at 12 weeks and at 6 months but more likely to display a lateral bias in paw use at 1 year. There was a significant positive correlation between cats' paw preferences at 6 months and at 1 year. Lateralized behavior was strongly sex related. Females had a greater preference for using their right paw; males were significantly more inclined to adopt their left. Analysis revealed no significant difference in the direction or strength of paw preferences of cats tested longitudinally or cross-sectionally at 6 months or 1 year of age. Findings indicate that cats develop paw preferences by 1 year and hint at a relative stability in preferred paw use over time. The strong sex effect observed strengthens the case for the influence of a biological mechanism in the emergence of motor asymmetry in cats.

Late glacial interhemispheric climate dynamics revealed in South African hyrax middens

Our ability to identify the timing and extent of past major climate fluctuations is central to understanding changes in the global climate system. Of the events that have occurred in recent geological time, the Younger Dryas (YD, 13-11.5 ka), an abrupt return to near-glacial conditions during the last glacial-interglacial transition (ca. 18-11.5 ka), is one of the most widely reported. While this event is apparent throughout the Northern Hemisphere (Peteet, 1995), evidence for its occurrence in the Southern Hemisphere remains equivocal due to a lack of well-dated terrestrial records. Here we report high-resolution stable carbon and nitrogen isotope records obtained from a rock hyrax midden, revealing the first unequivocal terrestrial manifestation of the YD from the southern African subtropics. These results provide key evidence for the relative influence of the YD, and suggest that a subtropical-temperate transition zone existed along the oceanic Subtropical Front (similar to 41 degrees S) across the Southern Hemisphere, with the Northern Hemisphere exerting a strong influence on all but the higher latitudes of the Southern Hemisphere after the Heinrich Stadial 1 (15 ka).