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)

In papers published between 1930 and 1935. Zermelo outlines a foundational program, with infinitary logic at its heart, that is intended to (1) secure axiomatic set theory as a foundation for arithmetic and analysis and (2) show that all mathematical propositions are decidable. Zermelo's theory of systems of infinitely long propositions may be termed "Cantorian" in that a logical distinction between open and closed domains plays a signal role. Well-foundedness and strong inaccessibility are used to systematically integrate highly transfinite concepts (...) of demonstrability and existence. Zermelo incompleteness is then the analogue of the Problem of Proper Classes, and the resolution of these two anomalies is similarly analogous. (shrink)

An idea attributable to Russell serves to extend Zermelo’s theory of systems of infinitely long propositions to infinitary relations. Specifically, relations over a given domain \ of individuals will now be identified with propositions over an auxiliary domain \ subsuming \. Three applications of the resulting theory of infinitary relations are presented. First, it is used to reconstruct Zermelo’s original theory of urelements and sets in a manner that achieves most, if not all, of his early aims. Second, the new (...) account of infinitary relations makes possible a concise characterization of parametric definability with respect to a purely relational structure. Finally, based on his foundational philosophy of the primacy of the infinite, Zermelo rejected Gödel’s First Incompleteness Theorem; it is shown that the new theory of infinitary relations can be brought to bear, positively, in that connection as well. (shrink)

On Zermelo's view, any mathematical theory presupposes a non-empty domain, the elements of which enjoy equal status; furthermore, mathematical axioms must be chosen from among those propositions that reflect the equal status of domain elements. As for which propositions manage to do this, Zermelo's answer is, those that are ?symmetric?, meaning ?invariant under domain permutations?. We argue that symmetry constitutes Zermelo's conceptual analysis of ?general proposition?. Further, although others are commonly associated with the extension of Klein's Erlanger Programme to logic, (...) Zermelo's name has a place in that story. (shrink)

Symmetric propositions over domain $\mathfrak{D}$ and signature $\Sigma = \langle R^{n_1}_1, \ldots, R^{n_p}_p \rangle$ are characterized following Zermelo, and a correlation of such propositions with logical type- $\langle \vec{n} \rangle$ quantifiers over $\mathfrak{D}$ is described. Boolean algebras of symmetric propositions over $\mathfrak{D}$ and Σ are shown to be isomorphic to algebras of logical type- $\langle \vec{n} \rangle$ quantifiers over $\mathfrak{D}$. This last result may provide empirical support for Tarski’s claim that logical terms over fixed domain are all and only those (...) invariant under domain permutations. (shrink)

What we call first‐order logic over fixed domain was initiated, in a certain guise, by Peirce around 1885 and championed, albeit in idiosyncratic form, by Zermelo in papers from the 1930s. We characterise such logics model‐ and proof‐theoretically and argue that they constitute exploration of a clearly circumscribed conception of domain‐dependent generality. Whereas a logic, or family of such, can be of interest for any of a variety of reasons, we suggest that one of those reasons might be that said (...) logic fosters some clarification regarding just what qualifies as a logical concept, a logical operation, or a logical law. (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)

Spillover occurs when one environmentally sustainable behaviour leads to another, often initiated by a behaviour change intervention. A number of studies have investigated positive and negative spillover effects, but empirical evidence is mixed, showing evidence for both positive and negative spillover effects, and lack of spillover altogether. Environmental identity has been identified as an influential factor for spillover effects. Building on identity process theory the current framework proposes that positive, negative, and a lack of spillover are determined by perceived threat (...) of initial behaviour and identity process mechanisms evaluating the behaviour. It is proposed, that an environmental behaviour change intervention may threaten one’s existing identities, leading to either (a) integration, (b) compartmentalisation, or (c) conflict between one’s environmental identity and non-environmental identities. Initial evidence for the proposed framework is based on a field intervention which included a meat reduction programme in a canteen of a medium size private sector company. Semi-structured interviews and an explorative visualisation method that aimed at assessing identity change were implemented with thirteen employees (i.e. intervention participants) before and after the intervention. The qualitative data was analysed by using thematic analysis via NVivo12. Results of the visualisation task and interview method provided initial evidence of direct and indirect positive contextual spillover effects, with comparatively less evidence a lack of spillover and a relative absence of reported negative spillover. This paper provides a novel theoretical approach, centred on identity process theory to enhance understanding of positive spillover, negative spillover, and the lack of spillover. (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 two-body quantum correlation is calculated for a particle reflecting from a moving mirror. Correlated interference results when the incident and reflected particle substates and their associated mirror substates overlap. Using the Copenhagen interpretation of measurement, an asynchronous joint probability density, which is a function both of the different positions and different times at which the particle and mirror are measured, is derived assuming that no interaction occurs between each measurement. Measurement of the particle first, in the correlated interference region, (...) results in a splitting of the mirror substate into ones which have and have not reflected the particle. An analog of the interference from the Doppler effect for only measurements of the particle, in this two-body system, is shown to be a consequence of the asynchronous measurement. The simplification obtained for a microscopic particle reflecting from a mesoscopic or macroscopic mirror is used to illustrate asynchronous correlation interferometry. In this case, the small displacement between these mirror states can yield negligible environmental decoherence times. In addition, interference of these mirror states does not vanish in the limit of large mirror mass due to the small momentum exchange in reflecting a microscopic particle. (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)

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)

In Canada, laws and policies consistently reject the commodification of human organs and tissues, and Canadian practice is consistent with international standards in this regard. Until the Assisted Human Reproduction Act of 2004, gamete donation in Canada was an exception: Canadians could pay and be paid open market rates for gametes for use in in vitro fertilization. As sections of the AHR Act forbidding payment for gametes and permitting only reimbursement of receipted expenses gradually came into effect in 2005, Canada (...) did away with this anomaly. Medical practice and legal prohibitions in assisted human reproduction are now consistent with other areas of medicine where tissues and organs are taken from one person to benefit others: Altruistic donation, rather than selling and buying, will be the norm. (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)

In recent years, we have seen a new concern with ethics training for research and development professionals. Although ethics training has become more common, the effectiveness of the training being provided is open to question. In the present effort, a new ethics training course was developed that stresses the importance of the strategies people apply to make sense of ethical problems. The effectiveness of this training was assessed in a sample of 59 doctoral students working in the biological and social (...) sciences using a pre–post design with follow-up and a series of ethical decision-making measures serving as the outcome variable. Results showed not only that this training led to sizable gains in ethical decision making but also that these gains were maintained over time. The implications of these findings for ethics training in the sciences are discussed. (shrink)

We live in a culture which, while largely dependent on science for its material welfare, is largely ignorant of the new ideas and perspectives on which science is based. This book examines the true significance of science and technology for society over the last three hundred years. Professor Hanbury Brown's insight and experience have resulted in a novel approach to the discussion of the cultural role of science. After reviewing the history of how science grew to be both useful to, (...) and feared by society, the book traces the same period in the context of new ideas and concepts in scientific research. Later chapters deal with society's current view of science and the need for attitudes to be changed, and then a discussion of the religious dimensions of science. This book aims to clear away some of the popular misconceptions about science and to put in their place a wider and deeper understanding of the nature of science and its value to society. (shrink)

Drawing from the development of individualism in western philosophy and American history, this book constructs a normative theory called authentic individualism. Using the precepts of that theory, it urges organizational leaders to change the way they think about their organizations and their organizations' social function. Students and scholars of political science, social science, public administration, moral theory and organizational theory will find this a useful work. Contents: Introduction to Individualism; PART ONE: A Model of the Individual from Western Philosophy; The (...) Individual of the Ancients; The Individual of the Dark Ages; The Individual of Modernity; PART TWO: A Model of the Individual in the United States; Rugged Individualism of the Revolutionary U.S.; Rational Individualism After Romanticism and Reform; Radical Individualism from Disillusionment and Loss of Faith; PART THREE: Synthesis of Philosophies Toward a More Socially Responsible Individualist in the Third Millennium; Need for a New World View; Changing the Paradigm; Soul of the Third Administrative State; Notes; Bibliography; Index. (shrink)

A photoaffinity analog of cGMP has been used to biochemically identify a new ligand-binding subunit of the retinal rod cGMP-activated ion channel, as well as amino acids in contact with cGMP in the original subunit. Covalent tethering of this probe to channels in excised menbrane patches has revealed a functional heteogeneity in the ligand-binding sites that may arise from the two biochemically identified subunits.