Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.

An ambiguity-based theory of the linguistic verbal joke in English

Instytut Filologii Angielskiej

Exploitation of linguistic ambiguity in Polish and English jokes

English & Polish jokes based on linguistic ambiguity are constrasted. Linguistic ambiguity results from a multiplicity of semantic interpretations motivated by structural pattern. The meanings can be "translated" either by variations of the corresponding minimal strings or by specifying the type & extent of modification needed between the two interpretations. C. F. Hockett's (1972) translatability notion that a joke is linguistic if it cannot readily be translated into other languages without losing its humor is used to interpret some cross-linguistic jokes. It is claimed that additional intralinguistic criteria are needed to classify jokes. By using a syntactic representation, the humor can be explained & compared cross-linguistically. Since the mapping of semantic values onto lexical units is highly language specific, translatability is much less frequent with lexical ambiguity. Similarly, phonological jokes are not usually translatable. Pragmatic ambiguity can be translated on the basis of H. P. Grice's (1975) cooperative principle of conversation that calls for discourse interpretations. If the distinction between linguistic & nonlinguistic jokes is based on translatability, pragmatic jokes must be excluded from the classification. Because of their universality, pragmatic jokes should be included into the linguistic classification by going beyond the translatability criteria & using intralinguistic features to describe them.

Ambiguity-generating devices in linguistic verbal jokes

Unpublished paper, written in 1996.

Temporal Dynamics of Decision-Making during Motion Perception in the Visual Cortex

How does the brain make decisions? Speed and accuracy of perceptual decisions covary with certainty in the input, and correlate with the rate of evidence accumulation in parietal and frontal cortical "decision neurons." A biophysically realistic model of interactions within and between Retina/LGN and cortical areas V1, MT, MST, and LIP, gated by basal ganglia, simulates dynamic properties of decision-making in response to ambiguous visual motion stimuli used by Newsome, Shadlen, and colleagues in their neurophysiological experiments. The model clarifies how brain circuits that solve the aperture problem interact with a recurrent competitive network with self-normalizing choice properties to carry out probablistic decisions in real time. Some scientists claim that perception and decision-making can be described using Bayesian inference or related general statistical ideas, that estimate the optimal interpretation of the stimulus given priors and likelihoods. However, such concepts do not propose the neocortical mechanisms that enable perception, and make decisions. The present model explains behavioral and neurophysiological decision-making data without an appeal to Bayesian concepts and, unlike other existing models of these data, generates perceptual representations and choice dynamics in response to the experimental visual stimuli. Quantitative model simulations include the time course of LIP neuronal dynamics, as well as behavioral accuracy and reaction time properties, during both correct and error trials at different levels of input ambiguity in both fixed duration and reaction time tasks. Model MT/MST interactions compute the global direction of random dot motion stimuli, while model LIP computes the stochastic perceptual decision that leads to a saccadic eye movement.

A soft robust model for optimization under ambiguity

In this paper, we propose a framework for robust optimization that relaxes the standard notion of robustness by allowing the decision maker to vary the protection level in a smooth way across the uncertainty set. We apply our approach to the problem of maximizing the expected value of a payoff function when the underlying distribution is ambiguous and therefore robustness is relevant. Our primary objective is to develop this framework and relate it to the standard notion of robustness, which deals with only a single guarantee across one uncertainty set. First, we show that our approach connects closely to the theory of convex risk measures. We show that the complexity of this approach is equivalent to that of solving a small number of standard robust problems. We then investigate the conservatism benefits and downside probability guarantees implied by this approach and compare to the standard robust approach. Finally, we illustrate theme thodology on an asset allocation example consisting of historical market data over a 25-year investment horizon and find in every case we explore that relaxing standard robustness with soft robustness yields a seemingly favorable risk-return trade-off: each case results in a higher out-of-sample expected return for a relatively minor degradation of out-of-sample downside performance. © 2010 INFORMS.

Chimpanzees and bonobos distinguish between risk and ambiguity.

Although recent research has investigated animal decision-making under risk, little is known about how animals choose under conditions of ambiguity when they lack information about the available alternatives. Many models of choice behaviour assume that ambiguity does not impact decision-makers, but studies of humans suggest that people tend to be more averse to choosing ambiguous options than risky options with known probabilities. To illuminate the evolutionary roots of human economic behaviour, we examined whether our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), share this bias against ambiguity. Apes chose between a certain option that reliably provided an intermediately preferred food type, and a variable option that could vary in the probability that it provided a highly preferred food type. To examine the impact of ambiguity on ape decision-making, we interspersed trials in which chimpanzees and bonobos had no knowledge about the probabilities. Both species avoided the ambiguous option compared with their choices for a risky option, indicating that ambiguity aversion is shared by humans, bonobos and chimpanzees.

The comparative advantage of the public sector in the development of urban water supply

This paper addresses the potential of public water operations in achieving developmental goals such as the Millennium Development Goals, and argues that the public sector has a comparative advantage in developing water services. The global importance of the public sector in urban water supply is examined through a review of current practice in the world's largest cities, including operational presence and distribution and ongoing trends. Empirical evidence shows that, in transition and developing countries, public operators are capable of undergoing successful reform. One explanatory factor is proposed to be the creation through the public sphere of highly interconnected networks among stakeholders. Such accountability networks act as vehicles for the generation and distribution of public knowledge among stakeholders, which in turn inform rational decision making on the reform and management of operations.

Do dynamic work instructions provide an advantage over static instructions in a small scale assembly task?

Recent studies exploring the effects of instructional animations on learning compared to static graphics have yielded mixed results. Few studies have explored their effectiveness in portraying procedural-motor information. Opportunities exist within an applied (manufacturing) context for instructional animations to be used to facilitate build performance on an assembly line. The present study compares build time performance across successive builds when using animation, static diagrams or text instructions to convey an assembly sequence for a handheld device. Although an immediate facilitating effect of animation was found, yielding a significantly faster build time for Build 1, this advantage had disappeared by Build 3. (C) 2009 Elsevier Ltd. All rights reserved.