Cell adhesion complexes are critical for the physical coordination of cell–cell interactions and the morphogenesis of tissues and organs. Many adhesion receptors are anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) moiety and are thereby partitioned into membrane rafts. In this review, we focus on reciprocal interactions between rafts and adhesion molecules, leading to receptor clustering and raft expansion and stability. A model for a three‐stage adhesion complex assembly process is also proposed. First, GPI‐anchored adhesion molecules are recruited into (...) rafts, which in turn promote receptor cis‐oligomerization and thereby produce precursory complexes primed for avid trans‐interactions. Second, trans‐interactions of the receptors cross‐link and stabilize large amalgams of rafts at sites of adhesion complex assembly. Finally, the enlarged and stabilized rafts acquire enhanced abilities to recruit the cytoskeleton and induce signaling. This process exemplifies how the domain structure of the plasma membrane can impact the function of its receptors. BioEssays 24:996–1003, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Risk communicators often need to communicate probabilistic predictions. On occasion, an event with 10% likelihood will occur, or one with 90% likelihood will not – a probabilistically unexpected ou...

Most previous works on responsible conduct of research have focused on good practices in laboratory experiments. Because computation now rivals experimentation as a mode of scientific research, we sought to identify the responsibilities of researchers who develop or use computational modeling and simulation. We interviewed nineteen experts to collect examples of ethical issues from their experiences in conducting research with computational models. We gathered their recommendations for guidelines for computational research. Informed by these interviews, we describe the respective professional responsibilities (...) of developers and users of computational models in research. In particular, we examine whether developers should disclose the full computational codes, and we explain how developers and users should minimize harms from improper uses of models. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

This paper posits that ethical leadership increases important organizational and individual outcomes by reducing politics in the workplace. Specifically, we propose that perceptions of organizational politics serve as a mechanism through which ethical leadership affects outcomes. We further argue that the modeled relationships are moderated by political skill. By means of data from 136 matched pairs of supervisors and subordinates employed by a state agency in the southern US, we found support for our predictions. Specifically, we found that perceptions of (...) organizational politics fully mediated the relationship between perceptions of ethical leadership and helping and promotability ratings. In addition, political skill was found to moderate the direct and indirect effects. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

To what extent should scientists, doctors and the community be constrained in their decision-making by a duty to posterity? How should we as a community balance our desire to benefit the present generation against the need not to irretrievably harm our successors? These questions are discussed with particular reference to genetic research and treatment that may have great potential for people suffering from genetic disease but may cause inherited changes in future generations, either deliberately or inadvertently. We conclude that the (...) community should take account of the interests of its successors but this should not immobilise us in the decisions we make for the present. (shrink)

In response to its current crisis, scholars call for the revitalisation of democracy through democratic innovations. While they make ample use of life metaphors describing democracy as a living organism, no comprehensive understanding of ‘life’ has been established within democratic theory. The Black Lives Matter (BLM) movement articulates the urgency of refocusing on life and its meaning through radical democratic practice. This article employs a grounded theory approach, enriched with participatory methods, to develop a radical democratic concept of life in (...) conversation with BLM. It conceptualises life as the existence of a perspective that constantly transforms through its fundamental interconnectedness. Building on this concept, the article outlines four principles of a living democracy that go beyond the revitalisation discourse. A living democracy (1) safeguards the existence of all humans and nonhumans, (2) nurtures a diversity of perspectives, (3) fosters social and planetary connectivity, and (4) enables self- and collective transformation. (shrink)

Body integrity identity disorder is a very rare condition in which people experience long-standing anguish because there is a mismatch between their bodies and their internal image of how their bodies should be. Most typically, these people are deeply distressed by the presence of what they openly acknowledge as a perfectly normal leg. Some with the condition request that their limb be amputated. 1 We and others have argued that such requests should be acceded to in carefully selected patients.1–4 Consistent (...) with this view, a group at the University of Sydney is developing a programme to better understand and treat BIID and to offer amputation if appropriate. In a recent paper, Patrone argues that such amputations should be prohibited.5 He suggests that authors supporting amputation in BIID depend on analogies with more familiar conditions and then claim that the ‘the desires, choices and requests of BIID patients should be held to exactly the same standards and treated with exactly the same respect as the desires, choices and requests of any more conventional patient’.5 He believes that these analogies are invalid and that therefore the arguments for amputation are invalid.Patrone concentrates a great deal upon whether a decision to have a particular medical intervention is to be regarded as ‘rational’. Unfortunately, he makes no attempt to define what he …. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

In this essay Harry Boyte and Margaret Finders argue that addressing the “shrinkage” of education and democracy requires acting politically to reclaim and augment Deweyan agency-focused concepts of democracy and education. Looking at agency from the vantage of civic studies, which advances a politics of agency — a citizen politics that is different from ideological politics — and citizens as cocreators of political communities, Boyte and Finders explore the technocratic trends that have eclipsed agency. These disempower educators, students, and communities. (...) Using the case study of the youth empowerment initiative Public Achievement and its translation into the Special Education Program and partnerships of Augsburg College, the authors conclude with an examination of how agentic practices have survived in “shadow spaces” in schools, how such spaces might be turned into “free spaces” for democratic change, and how teacher education needs to prepare “citizen teachers” as well as promoting pedagogies of empowerment. These suggest grounds for a movement of hope and democratic change. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

Do the rich descriptions and narrative shapings of literature provide a valuable resource for readers, writers, philosophers, and everyday people to imagine and confront the ultimate questions of life? Do the human activities of storytelling and complex moral decision-making have a deep connection? What are the moral responsibilities of the artist, critic, and reader? What can religious perspectives—from Catholic to Protestant to Mormon—contribute to literary criticism? Thirty well known contributors reflect on these questions, including iterary theorists Marshall Gregory, James Phelan, (...) and Wayne Booth; philosophers Martha Nussbaum, Richard Hart, and Nina Rosenstand; and authors John Updike, Charles Johnson, Flannery O'Connor, and Bernard Malamud. Divided into four sections, with introductory matter and questions for discussion, this accessible anthology represents the most crucial work today exploring the interdisciplinary connections between literature, religion and philosophy. (shrink)

Background: Pulsed dye laser is the gold standard for treatment of port-wine stain birthmarks but multiple treatments are required and complete resolution is often not achieved. Posttreatment vessel recurrence is thought to be a factor that limits efficacy of PDL treatment of PWS. Imiquimod 5% cream is an immunomodulator with antiangiogenic effects. Objective: We sought to determine if application of imiquimod 5% cream after PDL improves treatment outcome. Methods: Healthy individuals with PWS were treated with PDL and then randomized to (...) apply posttreatment placebo or imiquimod 5% cream for 8 weeks. Chromameter measurements for 57 PWS sites were taken at baseline and compared with measurements taken 8 weeks posttreatment. The Δa and ΔE were measured to quantify treatment outcome. Results: Two patients developed minor skin irritation. Other adverse effects were not noted. Average a was 0.43 for PDL + placebo sites and 1.27 for PDL + imiquimod sites indicating a greater reduction in erythema with imiquimod. Average E was 2.59 for PDL + placebo and 4.08 for PDL + imiquimod, again indicating a greater color improvement with imiquimod. Limitations: Effects were evaluated after a single treatment and duration of effect is unknown. Conclusion: Combined selective photothermolysis and antiangiogenic therapy may enhance PWS treatment efficacy. © 2011 by the American Academy of Dermatology, Inc. (shrink)

The neural correlates of rapid eye movements (REMs) in sleep are extraordinarily robust; including REM-locked activation in the retrosplenial cortex, the supplementary eye field and areas overlapping cholinergic basal nucleus. The phenomenology of REMs speaks to the notion that perceptual experience in both sleep and wakefulness is a constructive process – in which we generate predictions of sensory inputs and then test those predictions through actively sampling the sensorium with eye movements. On this view, REMs during sleep may index an (...) internalized active sampling or ‘scanning’ of self-generated visual constructs that are not constrained by visual input. If this view is correct, it renders REMs an ideal probe to study consciousness as “an exclusively internal affair” (Metzinger 2009). In other words, REMs offer a probe of active inference – in the sense of predictive coding – when the brain is isolated from the sensorium in virtue of the natural blockade of sensory input during REM sleep. REMs are temporally precise events that enable powerful inferences based on timeseries analyses. As a natural, task-free probe, [REMs] could be used in non-compliant subjects, including infants and animals. In short, REM constitutes a promising probe to study the ontogenetic and phylogenetic development of consciousness and perhaps its abnormal development in schizophrenia and autism, which have been considered in terms of aberrant predictive coding. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)