We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

There are wide individual differences in the ability to detect a stimulus contingency embedded in a complex paradigm. The present study used a cognitive masking paradigm to better understand individual differences related to contingency learning. Participants were assessed on measures of electrodermal arousal and on working memory capacity before engaging in the contingency learning task. Contingency awareness was assessed both by trial-by-trial verbal reports obtained during the task and by a short post-task recognition questionnaire. Participants who became aware had fewer (...) non-specific skin conductance responses and tended to score higher on a digit span assessment. Skin conductance level was not significantly lower in the aware group than in the unaware group. These findings are consistent with studies showing that lower arousal and greater cognitive processing capacity facilitate conscious perception of a greater breadth of information within a scene or a task. (shrink)

Kinetic demixing in quaternary mixed oxides has not been investigated previously, either theoretically or experimentally. In this theoretical study, we derive simple and exact analytical expressions that describe the steady-state cation concentration profiles resulting from kinetic demixing in mixed oxides of the O type. The concentration profiles are expressed in terms of cation-vacancy exchange frequency ratios. We assume a random distribution of cations and make use of the Moleko-Allnatt exact sum-rule expression relating the phenomenological coefficients in the ternary random alloy (...) to the vacancy mechanism operative. We employ Monte Carlo simulation of kinetic demixing to verify the result of the analysis. We discuss how kinetic demixing profiles can be processed to obtain atom-vacancy exchange frequency ratios. We also discuss how atom-vacancy exchange frequencies themselves might be obtained from available diffusivities in the quaternary oxide. (shrink)

Sterols and the reductant nicotinamide adenine dinucleotide phosphate (NADPH), essential for eukaryotic life, arose because of, and as an adaptation to, rising levels of molecular oxygen (O2). Hence, the NADPH and O2‐intensive process of sterol biosynthesis is inextricably linked to redox status. In mammals, cholesterol biosynthesis is exquisitely regulated post‐translationally by multiple E3 ubiquitin ligases, with membrane associated Really Interesting New Gene (RING) C3HC4 finger 6 (MARCHF6) degrading at least six enzymes in the pathway. Intriguingly, all these MARCHF6‐dependent enzymes require (...) NADPH. Moreover, MARCHF6 is activated by NADPH, although what this means for control of cholesterol synthesis is unclear. Indeed, this presents a paradox for how NADPH regulates this vital pathway, since NADPH is a cofactor in cholesterol biosynthesis and yet, low levels of NADPH should spare cholesterol biosynthesis enzymes targeted by MARCHF6 by reducing its activity. We speculate MARCHF6 helps mammalian cells adapt to oxidative stress (signified by low NADPH levels) by reducing degradation of cholesterogenic enzymes, thereby maintaining synthesis of protective cholesterol. (shrink)

Despite the lack of invariance problem (the many‐to‐many mapping between acoustics and percepts), human listeners experience phonetic constancy and typically perceive what a speaker intends. Most models of human speech recognition (HSR) have side‐stepped this problem, working with abstract, idealized inputs and deferring the challenge of working with real speech. In contrast, carefully engineered deep learning networks allow robust, real‐world automatic speech recognition (ASR). However, the complexities of deep learning architectures and training regimens make it difficult to use them to (...) provide direct insights into mechanisms that may support HSR. In this brief article, we report preliminary results from a two‐layer network that borrows one element from ASR, long short‐term memory nodes, which provide dynamic memory for a range of temporal spans. This allows the model to learn to map real speech from multiple talkers to semantic targets with high accuracy, with human‐like timecourse of lexical access and phonological competition. Internal representations emerge that resemble phonetically organized responses in human superior temporal gyrus, suggesting that the model develops a distributed phonological code despite no explicit training on phonetic or phonemic targets. The ability to work with real speech is a major advance for cognitive models of HSR. (shrink)

In his article ‘Did the Athenians Regard Seduction as a Worse Crime than Rape?’, CQ 40, 370–7, Edward M. Harris rightly casts doubt on the value of Lysias 1.30–5, which has generally been accepted as evidence that the Athenians did indeed regard seduction as the worse of the two crimes. Euphiletos in this speech is defending himself on a charge of murder, and, as Harris says, ‘Euphiletus’ presentation of the Athenian statutes regarding rape and seduction is dictated by the rhetorical (...) constraints of his case. It is not a reflection of widely held social attitudes.'. (shrink)

At the forefront of international concerns about global legislation and regulation, a host of noted environmentalists and business ethicists examine ethical issues in consumption from the points of view of environmental sustainability, economic development, and free enterprise.