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  • MEDLINE/PubMed (NLM)  (1,031)
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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 03 July 2012, Vol.109(27), pp.10990-5
    Description: Chemorepellants may play multiple roles in physiological and pathological processes. However, few endogenous chemorepellants have been identified, and how they function is unclear. We found that the autocrine signal AprA, which is produced by growing Dictyostelium discoideum cells and inhibits their proliferation, also functions as a chemorepellant. Wild-type cells at the edge of a colony show directed movement outward from the colony, whereas cells lacking AprA do not. Cells show directed movement away from a source of recombinant AprA and dialyzed conditioned media from wild-type cells, but not dialyzed conditioned media from aprA(-) cells. The secreted protein CfaD, the G protein Gα8, and the kinase QkgA are necessary for the chemorepellant activity of AprA as well as its proliferation-inhibiting activity, whereas the putative transcription factor BzpN is dispensable for the chemorepellant activity of AprA but necessary for inhibition of proliferation. Phospholipase C and PI3 kinases 1 and 2, which are necessary for the activity of at least one other chemorepellant in Dictyostelium, are not necessary for recombinant AprA chemorepellant activity. Starved cells are not repelled by recombinant AprA, suggesting that aggregation-phase cells are not sensitive to the chemorepellant effect. Cell tracking indicates that AprA affects the directional bias of cell movement, but not cell velocity or the persistence of cell movement. Together, our data indicate that the endogenous signal AprA acts as an autocrine chemorepellant for Dictyostelium cells.
    Keywords: Chemotaxis -- Physiology ; Dictyostelium -- Metabolism ; Protozoan Proteins -- Metabolism ; Signal Transduction -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Cognition, December 2015, Vol.145, pp.30-42
    Description: Past work has demonstrated that people’s moral judgments can influence their judgments in a number of domains that might seem to involve straightforward matters of fact, including judgments about freedom, causation, the doing/allowing distinction, and intentional action. The present studies explore whether the effect of morality in these four domains can be explained by changes in the relevance of alternative possibilities. More precisely, we propose that moral judgment influences the degree to which people regard certain alternative possibilities as relevant, which in turn impacts intuitions about freedom, causation, doing/allowing, and intentional action. Employing the stimuli used in previous research, Studies 1a, 2a, 3a, and 4a show that the relevance of alternatives is influenced by moral judgments and mediates the impact of morality on non-moral judgments. Studies 1b, 2b, 3b, and 4b then provide direct empirical evidence for the link between the relevance of alternatives and judgments in these four domains by manipulating (rather than measuring) the relevance of alternative possibilities. Lastly, Study 5 demonstrates that the critical mechanism is not whether alternative possibilities are considered, but whether they are regarded as . These studies support a unified framework for understanding the impact of morality across these very different kinds of judgments.
    Keywords: Morality ; Alternative Possibilities ; Modality ; Psychology
    ISSN: 0010-0277
    E-ISSN: 18737838
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  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 02 May 2017, Vol.114(18), pp.4649-4654
    Description: The capacity for representing and reasoning over sets of possibilities, or modal cognition, supports diverse kinds of high-level judgments: causal reasoning, moral judgment, language comprehension, and more. Prior research on modal cognition asks how humans explicitly and deliberatively reason about what is possible but has not investigated whether or how people have a default, implicit representation of which events are possible. We present three studies that characterize the role of implicit representations of possibility in cognition. Collectively, these studies differentiate explicit reasoning about possibilities from default implicit representations, demonstrate that human adults often default to treating immoral and irrational events as impossible, and provide a case study of high-level cognitive judgments relying on default implicit representations of possibility rather than explicit deliberation.
    Keywords: High-Level Cognition ; Modality ; Morality ; Norms ; Possibility ; Cognition ; Judgment ; Morals
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 4
    Language: English
    In: Cognition, 2011, Vol.119(2), pp.166-178
    Description: When we evaluate moral agents, we consider many factors, including whether the agent acted freely, or under duress or coercion. In turn, moral evaluations have been shown to influence our (non-moral) evaluations of these same factors. For example, when we judge an agent to have acted immorally, we are subsequently more likely to judge the agent to have acted freely, not under force. Here, we investigate the cognitive signatures of this effect in interpersonal situations, in which one agent (“forcer”) forces another agent (“forcee”) to act either immorally or morally. The structure of this relationship allowed us to ask questions about both the “forcer” and the “forcee.” Paradoxically, participants judged that the “forcer” forced the “forcee” to act immorally (i.e. X forced Y), but that the “forcee” was not forced to act immorally (i.e. Y was not forced by X). This pattern obtained only for human agents who acted intentionally. Directly changing participants’ focus from one agent to another (forcer versus forcee) also changed the target of moral evaluation and therefore force attributions. The full pattern of judgments may provide a window into motivated moral reasoning and focusing bias more generally; participants may have been motivated to attribute greater force to the immoral forcer and greater freedom to the immoral forcee.
    Keywords: Morality ; Motivated Cognition ; Force ; Focusing ; Counterfactual Thinking ; Psychology
    ISSN: 0010-0277
    E-ISSN: 18737838
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  • 5
    Language: English
    In: Journal of Experimental Child Psychology, January 2018, Vol.165, pp.161-182
    Description: Young children have difficulty in distinguishing events that violate physical laws (impossible events) from those that violate mere physical regularities (improbable events). They judge both as “impossible.” Young children also have difficulty in distinguishing events that violate moral laws (immoral events) from events that violate mere social regularities (unconventional events). They judge both as “wrong.” In this set of studies, we explored the possibility that both difficulties arise from a more general deficit in cognition, or the way in which children represent and reason about possibilities. Participants (80 children aged 3–10 years and 101 adults) were shown impossible, improbable, unconventional, and immoral events and were asked to judge whether the events could occur in real life and whether they would be okay to do. Preschool-aged children not only had difficulty distinguishing law-violating events from regularity-violating events but also had difficulty distinguishing the two modal questions themselves, judging physically abnormal events (e.g., floating in the air) as immoral and judging socially abnormal events (e.g., lying to a parent) as impossible. These findings were replicated in a second study where participants (74 children and 78 adults) judged whether the events under consideration would require magic (a specific consequence of impossibility) or would require punishment (a specific consequence of impermissibility). Our findings imply that young children’s modal representations clearly distinguish abnormal events from ordinary events but do not clearly distinguish different types of abnormal events from each other. That is, the distinction between whether an event occur and whether an event occur must be learned.
    Keywords: Moral Judgment ; Possibility Judgment ; Social Reasoning ; Physical Reasoning ; Modality ; Conceptual Development ; Social Welfare & Social Work ; Psychology
    ISSN: 0022-0965
    E-ISSN: 1096-0457
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  • 6
    Language: English
    In: Journal of Physics: Condensed Matter, 2011, Vol.23(19), p.194111 (9pp)
    Description: Using fundamental measure density functional theory we investigate paranematicnematic and nematicnematic phase coexistence in binary mixtures of circular platelets with vanishing thicknesses. An external magnetic field induces uniaxial alignment and acts on the platelets with a strength that is taken to scale with the platelet area. At particle diameter ratio = 1.5 the system displays paranematicnematic coexistence. For = 2, demixing into two nematic states with different compositions also occurs, between an upper critical point and a paranematicnematicnematic triple point. Increasing the field strength leads to shrinking of the coexistence regions. At high enough field strength a closed loop of immiscibility is induced and phase coexistence vanishes at a double critical point above which the system is homogeneously nematic. For = 2.5, besides paranematicnematic coexistence, there is nematicnematic coexistence which persists and hence does not end in a critical point. The partial orientational order parameters along the binodals vary strongly with composition and connect smoothly for each species when closed loops of immiscibility are present in the corresponding phase diagram.
    Keywords: Condensed Matter - Soft Condensed Matter;
    ISSN: 0953-8984
    E-ISSN: 1361-648X
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  • 7
    Language: English
    In: Journal of Environmental Management, 2011, Vol.92(2), pp.284-289
    Description: Rivers crossing coastal plains are often inefficient conveyors of sediment, so that changes in upstream sediment dynamics are not evident at the river mouth. Extensive accommodation space and low stream power often result in extensive alluvial storage upstream of estuaries and correspondingly low sediment loads at the river mouth. However, gaging stations with sediment records are typically well upstream of the coast, and thus tend to overestimate sediment yields by under-representing the lower coastal plain and because there is often a net loss of sediment in lower coastal plain reaches. Studies of alluvial sediment storage have generally focused on accommodation space, but, using examples from Texas, we show that low transport capacity controlled largely by slope is a crucial factor.
    Keywords: Sediment Flux ; Low Energy Rivers ; Texas ; Dams ; Alluvial Storage ; Environmental Sciences ; Economics
    ISSN: 0301-4797
    E-ISSN: 1095-8630
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  • 8
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(5), p.e96633
    Description: In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal transduction pathways associated with AprA and CfaD are not clear, and little is known about how AprA affects the cytoskeleton to regulate cell movement. We found that the p21-activated kinase (PAK) family member PakD is required for both the proliferation-inhibiting activity of AprA and CfaD and the chemorepellent activity of AprA. Similar to cells lacking AprA or CfaD, cells lacking PakD proliferate to a higher cell density than wild-type cells. Recombinant AprA and CfaD inhibit the proliferation of wild-type cells but not cells lacking PakD. Like AprA and CfaD, PakD affects proliferation but does not significantly affect growth (the accumulation of mass) on a per-nucleus basis. In contrast to wild-type cells, cells lacking PakD are not repelled from a source of AprA, and colonies of cells lacking PakD expand at a slower rate than wild-type cells, indicating that PakD is required for AprA-mediated chemorepulsion. A PakD-GFP fusion protein localizes to an intracellular punctum that is not the nucleus or centrosome, and PakD-GFP is also occasionally observed at the rear cortex of moving cells. Vegetative cells lacking PakD show excessive actin-based filopodia-like structures, suggesting that PakD affects actin dynamics, consistent with previously characterized roles of PAK proteins in actin regulation. Together, our results implicate PakD in AprA/CfaD signaling and show that a PAK protein is required for proper chemorepulsive cell movement in Dictyostelium.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 9
    In: Neurology, 2014, Vol.82(1), pp.77-79
    Description: Randomization is the standard means for addressing known and unknown confounders within the patient population in clinical trials. Although random assignment to treatment arms on a 1:1 basis has long been the norm, many 2-armed confirmatory trials now use unequal allocation schemes where the number of patients receiving investigational interventions exceeds those in the comparator arm. In what follows, we offer 3 arguments for why investigators, institutional review boards, and data and safety monitoring boards should exercise caution when planning or reviewing 2-armed confirmatory trials involving unequal allocation ratios. We close by laying out some of the conditions where uneven allocation can be justified ethically.
    Keywords: Medicine;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 10
    Language: English
    In: Physical review. E, Statistical, nonlinear, and soft matter physics, April 2010, Vol.81(4 Pt 1), pp.041401
    Description: We investigate isotropic-isotropic, isotropic-nematic, and nematic-nematic phase coexistence in binary mixtures of circular platelets with vanishing thickness, continuous rotational degrees of freedom, and radial size ratios lambda up to 5. A fundamental measure density functional theory, previously used for the one-component model, is presented and results are compared against those from Onsager theory as a benchmark. For lambdaor=2, we find that demixing into two nematic states becomes stable and an isotropic-nematic-nematic triple point can occur. Fundamental measure theory gives a smaller isotropic-nematic biphasic region than Onsager theory and locates the transition at lower densities. Furthermore, nematic-nematic demixing occurs over a larger range of compositions at a given value of lambda than found in Onsager theory. Both theories predict the same topologies of the phase diagrams. The partial nematic order parameters vary strongly with composition and indicate that the larger particles are more strongly ordered than the smaller particles.
    Keywords: Condensed Matter - Soft Condensed Matter;
    ISSN: 15393755
    E-ISSN: 1550-2376
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