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)

A novel conceptual framework is introduced for the Complexity Levels Theory in a Categorical Ontology of Space and Time. This conceptual and formal construction is intended for ontological studies of Emergent Biosystems, Super-complex Dynamics, Evolution and Human Consciousness. A claim is defended concerning the universal representation of an item’s essence in categorical terms. As an essential example, relational structures of living organisms are well represented by applying the important categorical concept of natural transformations to biomolecular reactions and relational structures that (...) emerge from the latter in living systems. Thus, several relational theories of living systems can be represented by natural transformations of organismic, relational structures. The ascent of man and other living organisms through adaptation, is viewed in novel categorical terms, such as variable biogroupoid representations of evolving species. Such precise but flexible evolutionary concepts will allow the further development of the unifying theme of local-to-global approaches to highly complex systems in order to represent novel patterns of relations that emerge in super- and ultra-complex systems in terms of compositions of local procedures. Solutions to such local-to-global problems in highly complex systems with ‘broken symmetry’ might be possible to be reached with the help of higher homotopy theorems in algebraic topology such as the generalized van Kampen theorems (HHvKT). Categories of many-valued, Łukasiewicz-Moisil (LM) logic algebras provide useful concepts for representing the intrinsic dynamic ‘asymmetry’ of genetic networks in organismic development and evolution, as well as to derive novel results for (non-commutative) Quantum Logics. Furthermore, as recently pointed out by Baianu and Poli (Theory and applications of ontology, vol 1. Springer, Berlin, in press), LM-logic algebras may also provide the appropriate framework for future developments of the ontological theory of levels with its complex/entangled/intertwined ramifications in psychology, sociology and ecology. As shown in the preceding two papers in this issue, a paradigm shift towards non-commutative, or non-Abelian, theories of highly complex dynamics—which is presently unfolding in physics, mathematics, life and cognitive sciences—may be implemented through realizations of higher dimensional algebras in neurosciences and psychology, as well as in human genomics, bioinformatics and interactomics. (shrink)

An overview of the following three related papers in this issue presents the Emergence of Highly Complex Systems such as living organisms, man, society and the human mind from the viewpoint of the current Ontological Theory of Levels. The ontology of spacetime structures in the Universe is discussed beginning with the quantum level; then, the striking emergence of the higher levels of reality is examined from a categorical—relational and logical viewpoint. The ontological problems and methodology aspects discussed in the first (...) two papers are followed by a rigorous paper based on Category Theory, Algebraic Topology and Logic that provides a conceptual and mathematical basis for a Categorical Ontology Theory of Levels. The essential links and relationships between the following three papers of this issue are pointed out, and further possible developments are being considered. (shrink)

A categorical, higher dimensional algebra and generalized topos framework for Łukasiewicz–Moisil Algebraic–Logic models of non-linear dynamics in complex functional genomes and cell interactomes is proposed. Łukasiewicz–Moisil Algebraic–Logic models of neural, genetic and neoplastic cell networks, as well as signaling pathways in cells are formulated in terms of non-linear dynamic systems with n-state components that allow for the generalization of previous logical models of both genetic activities and neural networks. An algebraic formulation of variable ‘next-state functions’ is extended to a Łukasiewicz–Moisil (...) Topos with an n-valued Łukasiewicz–Moisil Algebraic Logic subobject classifier description that represents non-random and non-linear network activities as well as their transformations in developmental processes and carcinogenesis. The unification of the theories of organismic sets, molecular sets and Robert Rosen’s (M,R)-systems is also considered here in terms of natural transformations of organismal structures which generate higher dimensional algebras based on consistent axioms, thus avoiding well known logical paradoxes occurring with sets. Quantum bionetworks, such as quantum neural nets and quantum genetic networks, are also discussed and their underlying, non-commutative quantum logics are considered in the context of an emerging Quantum Relational Biology. (shrink)

A novel conceptual framework is introduced for the Complexity Levels Theory in a Categorical Ontology of Space and Time. This conceptual and formal construction is intended for ontological studies of Emergent Biosystems, Super-complex Dynamics, Evolution and Human Consciousness. A claim is defended concerning the universal representation of an item’s essence in categorical terms. As an essential example, relational structures of living organisms are well represented by applying the important categorical concept of natural transformations to biomolecular reactions and relational structures that (...) emerge from the latter in living systems. Thus, several relational theories of living systems can be represented by natural transformations of organismic, relational structures. The ascent of man and other living organisms through adaptation, is viewed in novel categorical terms, such as variable biogroupoid representations of evolving species. Such precise but flexible evolutionary concepts will allow the further development of the unifying theme of local-to-global approaches to highly complex systems in order to represent novel patterns of relations that emerge in super- and ultra-complex systems in terms of compositions of local procedures. Solutions to such local-to-global problems in highly complex systems with ‘broken symmetry’ might be possible to be reached with the help of higher homotopy theorems in algebraic topology such as the generalized van Kampen theorems (HHvKT). Categories of many-valued, Łukasiewicz-Moisil (LM) logic algebras provide useful concepts for representing the intrinsic dynamic ‘asymmetry’ of genetic networks in organismic development and evolution, as well as to derive novel results for (non-commutative) Quantum Logics. Furthermore, as recently pointed out by Baianu and Poli (Theory and applications of ontology, vol 1. Springer, Berlin, in press), LM-logic algebras may also provide the appropriate framework for future developments of the ontological theory of levels with its complex/entangled/intertwined ramifications in psychology, sociology and ecology. As shown in the preceding two papers in this issue, a paradigm shift towards non-commutative, or non-Abelian, theories of highly complex dynamics—which is presently unfolding in physics, mathematics, life and cognitive sciences—may be implemented through realizations of higher dimensional algebras in neurosciences and psychology, as well as in human genomics, bioinformatics and interactomics. (shrink)

Properties sometimes attributed to the “particle” aspect of a neutron, e.g., mass and magnetic moment, cannot straightforwardly be regarded in the Bohm interpretation of quantum mechanics as localized at the hypothetical position of the particle. This is shown by examining a series of effects in neutron interferometry. A related thought-experiment also provides a variation of a recent demonstration that which-way detectors can appear to behave anomolously in the Bohm theory.

An overview of the following three related papers in this issue presents the Emergence of Highly Complex Systems such as living organisms, man, society and the human mind from the viewpoint of the current Ontological Theory of Levels. The ontology of spacetime structures in the Universe is discussed beginning with the quantum level; then, the striking emergence of the higher levels of reality is examined from a categorical—relational and logical viewpoint. The ontological problems and methodology aspects discussed in the first (...) two papers are followed by a rigorous paper based on Category Theory, Algebraic Topology and Logic that provides a conceptual and mathematical basis for a Categorical Ontology Theory of Levels. The essential links and relationships between the following three papers of this issue are pointed out, and further possible developments are being considered. (shrink)

Endosperm is emerging as a system for investigating the genetic control of wall placement and deposition in plant development. Development of endosperm progresses in distinct stages from a wall‐less syncytial stage to a cellular stage that is entirely typical of plant meristems where the division plane is predicted by a preprophase band of microtubules (PPB) and cytokinesis is completed by formation of a cell plate in association with a phragmoplast. Four developmentally different types of walls, each associated with a different (...) microtubule system, are sequentially produced: (1) free growing walls deposited in the absence of mitosis and phragmoplasts; (2) walls guided by cytoplasmic phragmoplasts formed adventitiously in the absence of mitosis; (3) walls formed by interzonal phragmoplasts in a cell cycle that lacks PPBs; and (4) wall deposition driven by interzonal phragmoplasts in a cycle that includes PPBs. We are using methods of differential screening to isolate cDNA clones corresponding in temporal and spatial pattern to the types of wall development, and are studying mutants for clues to the genetic controls of wall development. (shrink)

Stimuli such as surprised faces are ambiguous in that they are associated with both positive and negative outcomes. Interestingly, people differ reliably in whether they evaluate these and other ambiguous stimuli as positive or negative, and we have argued that a positive evaluation relies in part on a biasing of the appraisal processes via reappraisal. To further test this idea, we conducted two studies to evaluate whether increasing the cognitive accessibility of reappraisal through a brief emotion regulation task would lead (...) to an increase in positive evaluations of ambiguity. Supporting this prediction, we demonstrated that cuing reappraisal, but not in three other forms of emotion regulation (Study 1a-d; n = 120), increased positive evaluations of ambiguous faces. In a sign of robustness, we also found that the effect of reappraisal generalised from ambiguous faces to ambiguous scenes (Study 2; n = 34). Collectively, these findings suggest that reappraisal may play a key role in determining responses to ambiguous stimuli. We discuss these findings in the context of affective flexibility, and suggest that valence bias (i.e. the tendency to evaluate ambiguity more positively or negatively) represents a novel approach to measuring implicit emotion regulation. (shrink)

Next SectionIn an online study conducted separately in the UK and the US, participants rated the acceptability and fairness of four interventions: two types of financial incentives and two types of medical interventions. These were stated to be equally effective in improving outcomes in five contexts: weight loss and smoking cessation programmes, and adherence in treatment programmes for drug addiction, serious mental illness and physiotherapy after surgery. Financial incentives were judged less acceptable and to be less fair than medical interventions (...) across all five contexts. Context moderated the relative preference between rewards and penalties: participants from both countries favoured rewards over penalties in weight loss and treatment for serious mental illness. Only among US participants was this relative preference moderated by perceived responsibility of the target group. Overall, participants supported funding more strongly for interventions when they judged members of the target group to be less responsible for their condition, and vice versa. These results reveal a striking similarity in negative attitudes towards the use of financial incentives, rewards as well as penalties, in improving outcomes across a range of contexts, in the UK and the USA. The basis for such negative attitudes awaits further study. (shrink)

This chapter describes the potential far‐reaching consequences of contemplative higher education for the fields of science and medicine.

(Statement of Responsibility) by Timothy S. Huebner.