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)

We report evidence further supporting homology between proteins in the F1FO‐ATP synthetase and the bacterial flagellar motor (BFM). BFM proteins FliH, FliI, and FliJ have been hypothesized to be homologous to FO‐b + F1‐δ, F1‐α/β, and F1‐γ, with similar structure and interactions. We conduct a further test by constructing a gene order dataset, examining the order offliH,fliI, andfliJgenes across the phylogenetic breadth of flagellar and nonflagellar type 3 secretion systems, and comparing this to published surveys of gene order in the (...) F1FO‐ATP synthetase, its N‐ATPase relatives, and the bacterial/archaeal V‐ and A‐type ATPases. Strikingly, thefliHIJgene order was deeply conserved, with the few exceptions appearing derived, and exactly matching the widely conserved F‐ATPase gene orderatpFHAG, coding for subunits b‐δ‐α‐γ. The V/A‐type ATPases have a similar conserved gene order. Our results confirm homology between these systems, and suggest a rare case of synteny conserved over billions of years, predating the Last Universal Common Ancestor (LUCA). (shrink)

Covert behavior may also be strong behavior which cannot be overtly emitted because the proper circumstances are lacking. When we are strongly inclined to go skiing, although there is no snow, we say I would like to go skiing. It is not very  ...

The major contributions of operationism have been negative, largely because operationists failed to distinguish logical theories of reference from empirical accounts of language. Behaviorism never finished an adequate formulation of verbal reports and therefore could not convincingly embrace subjective terms. But verbal responses to private stimuli can arise as social products through the contingencies of reinforcement arranged by verbal communities.

Each of us is uniquely subject to certain kinds of stimulation from a small part of the universe within our skins. Mentalistic psychologies insist that other kinds of events, lacking the physical dimensions of stimuli, are accessible to the owner of the skin within which they occur. One solution often regarded as behavioristic, granting the distinction between public and private events and ruling the latter out of consideration, has not been successful. A science of behavior must face the problem of (...) privacy by dealing with events within the skin in their relation to behavior, without assuming they have a special nature or must be known in a special way. (shrink)

Human behavior is the joint product of (i) contingencies of survival responsible for natural selection, and (ii) contingencies of reinforcement responsible for the repertoires of individuals, including (iii) the special contingencies maintained by an evolved social environment. Selection by consequences is a causal mode found only in living things, or in machines made by living things. It was first recognized in natural selection: Reproduction, a first consequence, led to the evolution of cells, organs, and organisms reproducing themselves under increasingly diverse (...) conditions. The behavior functioned well, however, only under conditions similar to those under which it was selected.Reproduction under a wider range of consequences became possible with the evolution of processes through which organisms acquired behavior appropriate to novel environments. One of these, operant conditioning, is a second kind of selection by consequences: New responses could be strengthened by events which followed them. When the selecting consequences are the same, operant conditioning and natural selection work together redundantly. But because a species which quickly acquires behavior appropriate to an environment has less need for an innate repertoire, operant conditioning could replace as well as supplement the natural selection of behavior.Social behavior is within easy range of natural selection, because other members are one of the most stable features of the environment of a species. The human species presumably became more social when its vocal musculature came under operant control. Verbal behavior greatly increased the importance of a third kind of selection by consequences, the evolution of social environments or cultures. The effect on the group, and not the reinforcing consequences for individual members, is responsible for the evolution of culture. (shrink)

Behavior that solves a problem is distinguished by the fact that it changes another part of the solver's behavior and is strengthened when it does so. Problem solving typically involves the construction of discriminative stimuli. Verbal responses produce especially useful stimuli, because they affect other people. As a culture formulates maxims, laws, grammar, and science, its members behave more effectively without direct or prolonged contact with the contingencies thus formulated. The culture solves problems for its members, and does so by (...) transmitting the verbal discriminative stimuli called rules. Induction, deduction, and the construction of models are ways of producing rules. Behavior that solves a problem may result from direct shaping by contingencies or from rules constructed either by the problem solver or by others. Because different controlling variables are involved, contingency-shaped behavior is never exactly like rule-governed behavior. The distinction must take account of a system which establishes certain contingencies of reinforcement, such as some part of the natural environment, a piece of equipment, or a verbal community; the behavior shaped and maintained by these contingencies; rules, derived from the contingencies, which specify discriminative stimuli, responses, and consequences, and the behavior occasioned by the rules. (shrink)

We owe most scientific knowledge to methods of inquiry that are never formally analyzed. The analysis of behavior does not call for hypothetico-deductive methods. Statistics, taught in lieu of scientific method, is incompatible with major features of much laboratory research. Squeezing significance out of ambiguous data discourages the more promising step of scrapping the experiment and starting again. As a consequence, psychologists have taken flight from the laboratory. They have fled to Real People and the human interest of “real life,” (...) to Mathematical Models and the elegance of symbolic treatments, to the Inner Man and the explanatory preoccupation with inferred internal mechanisms, and to Laymanship and its appeal to “common sense.” An experimental analysis provides an alternative to these divertissements.The “theories” to which objection is raised here are not the basic assumptions essential to any scientific activity or statements that are not yet facts, but rather explanations which appeal to events taking place somewhere else, at some other level of observation, described in different terms, and measured, if at all, in different dimensions. Three types of learning theories satisfy this definition: physiological theories attempting to reduce behavior to events in the nervous system; mentalistic theories appealing to inferred inner events; and theories of the Conceptual Nervous System offered as explanatory models of behavior. It would be foolhardy to deny the achievements of such theories in the history of science. The question of whether they are necessary, however, has other implications.Experimental material in three areas illustrates the function of theory more concretely. Alternatives to behavior ratios, excitatory potentials, and so on demonstrate the utility of rate or probability of response as the basic datum in learning. Functional relations between behavior and environmental variables provide an account of why learning occurs. Activities such as preferring, choosing, discriminating, and matching can be dealt with solely in terms of behavior, without referring to processes in another dimensional system. The experiments are not offered as demonstrating that theories are not necessary but to suggest an alternative. Theory is possible in another sense. Beyond the collection of uniform relationships lies the need for a formal representation of the data reduced to a minimal number of terms. A theoretical construction may yield greater generality than any assemblage of facts; such a construction will not refer to another dimensional system. (shrink)

Mcguiness finds in the early wittgenstein a metaphysics similar to\nthat of nature mysticism. he discusses the relation between this\nkind of mysticism and wittgenstein's views on logic, ethics, aesthetics,\noptimism, solipsism, and 'living in the present.' he suggests that\nwittgenstein may have had some kind of mystical experience which\ninfluenced his early philosophy. (staff).

definitions and explanations frequently come together and permeate almost all fields of knowledge. This does not exclude mathematics, even when these definitions hold clear links and close connections with our physical world. Here we propose a rather different perspective. Making operational physical assumptions, we show how it is possible to rigorously reconstruct some features of both geometry and topology. Broadly speaking, assuming this operational and more concrete philosophy we not only are capable of defining primitive concepts like points, straight lines, (...) planes, angles and spaces, but we also go all the way up to more complex constructions. We show that within our method it is also possible to come up with what we call a compass-based topology as well as a normed and a metric space. We hope this operationalist point-of-view can assist other researchers and students to have a clearer understanding of these quite abstract concepts. (shrink)

Responses are strengthened by consequences having to do with the survival of individuals and species. With respect to the provenance of behavior, we know more about ontogenic than phylogenic contingencies. The contingencies responsible for unlearned behavior acted long ago. This remoteness affects our scientific methods, both experimental and conceptual. Until we have identified he variables responsible for an event, we tend to invent causes. Explanatory entities such as “instincts,” “drives,” and “traits” still survive. Unable to show how organisms can behave (...) effectively under complex circumstances, we endow them with special abilities permitting them to do so.Behavior exhibited by most members of a species is often accepted as inherited if all members were not likely to have been exposed to relevant ontogenic contingencies. When contingencies are not obvious, it is perhaps unwise to call any behavior either inherited or acquired, as the examples of churring in honey guides and following in imprinted ducklings show. Nor can the relative importance of phylogenic and ontogenic contingencies be argued from instances in which unlearned or learned behavior intrudes or dominates. Intrusions occur in both directions.Behavior influenced by its consequences seems directed toward the future, but only past effects are relevant. The mere fact that behavior is adaptive does not indicate whether phylogenic or ontogenic processes have been responsible for it. Examples include the several possible provenances of imitation, aggression, and communication. The generality of such concepts limits their usefulness. A more specific analysis is needed if we are to deal effectively with the two kinds of contingencies and their products. (shrink)

The year 1927 is a landmark in the evolution of physics—the year which saw the obsequies of the notion of causality. To avoid misconceptions, it should not be thought that the concept fell a victim to the unbridled antipathy of certain physicists or their indulgence in fancies. The truth is that men of science came, very reluctantly and almost against their will, to recognize the impossibility of giving a coherent causal description of the happenings on the atomic scale, though some (...) of them—curiously enough, amongst them Planck, Einstein, de Broglie, Schrödinger—could never bring themselves to accept wholeheartedly so drastic a renunciation of classical ideals. (shrink)