Stimulation of airway myocytes by contractile agents such as acetylcholine (ACh) activates a Ca2+-activated Cl– current (IClCa) which may play a key role in calcium homeostasis of airway myocytes and hence in airway reactivity. The aim of the present study was to model IClCa in airway smooth muscle cells using a computerised model previously designed for simulation of cardiac myocyte functioning. Modelling was based on a simple resistor-battery permeation model combined with multiple binding site activation by calcium. In order to (...) validate the model, a combination of equations, used to mimic [Ca2+]i response to ACh stimulation, were incorporated into the model. The results indicate that the model developed in this article accounts for experimental recordings and electrophysiological characteristics of this current in airway smooth muscle cells, with parameter values consistent with those calculated from experimental data. Such a model may thus be used to predict IClCa functioning, though additional experimental data from airway myocytes would be useful to more accurately determine some parameter values of the model. (shrink)

This ambitious book explores the relationship between time and history and shows how an appreciation of long-term time helps to make sense of the past. The book is devoted to a wide-ranging analysis of the way different societies have conceived and interpreted time, and it develops a theory of the threefold roles of continuity, gradual change, and revolution which together form a "braided" history. Linking the interpretative chapters are intriguing brief expositions on time travel, time cycles, time lines, and time (...) pieces, showing the different ways in which human history has been located in time. In its global approach the book is part of the new shift toward “big history,” in which traditional period divisions are challenged in favor of looking at the entire past of the world from start to end. The approach is thematic. The result is a view of world history in which outcomes are shown to be explicable, once they happen, but not necessarily predictable before they do. This book will inform the work of historians of all periods and at all levels, and contributes to the current reconsideration of traditional period divisions (such as Modernity and Postmodernity), which the author finds outmoded. (shrink)

My ultimate goal in this paper is to illuminate, from a naturalistic point of view, the significance of the application of mathematics in the natural sciences for the practice of contemporary set theory.

Juliette Kennedy’s new book brims with intriguing ideas. I don’t understand all of them, and I’m not convinced that the ones I do understand all fit together, b.

How did humans respond to the eighteenth-century discovery of countless new species of animals? This book explores the gamut of human-animal interactions: from love to cultural identifications, moral reflections, philosophical debates, classification systems, mechanical copies, insults and literary creativity.

Sleep enhances integration across multiple stimuli, abstraction of general rules, insight into hidden solutions and false memory formation. Newly learned information is better assimilated if compatible with an existing cognitive framework or schema. This article proposes a mechanism by which the reactivation of newly learned memories during sleep could actively underpin both schema formation and the addition of new knowledge to existing schemata. Under this model, the overlapping replay of related memories selectively strengthens shared elements. Repeated reactivation of memories in (...) different combinations progressively builds schematic representations of the relationships between stimuli. We argue that this selective strengthening forms the basis of cognitive abstraction, and explain how it facilitates insight and false memory formation. (shrink)

The underrepresentation of females in mathematics-related fields may be explained by gender differences in mathematics self-concept (rather than ability) favoring males. Mathematics self-concept typically declines with student age, differs with student ethnicity, and is sensitive to teacher influence in early schooling. We investigated whether change in mathematics self-concept occurred within the context of a longitudinal intervention to raise and sustain teacher expectations of student achievement. This experimental study was conducted with a large sample of New Zealand primary school students and (...) their teachers. Data were analyzed using longitudinal multilevel modelling with mathematics self-concept as the dependent variable and time (which represents students’ increasing age each year), gender, and ethnicity entered as predictors and achievement in mathematics included as a control variable. Interaction terms were also explored to investigate changes over time for different groups. All students demonstrated a small increase in mathematics self-concept over the three-year period of the current study but mathematics self-concept was consistently greater for boys than girls. Māori, Asian, and Other students’ initial mathematics self-concept was higher than that of New Zealand European and Pacific Islanders’ (after controlling for achievement differences). However, a statistically significant decline in mathematics self-concept occurred for Māori students alone by the end of the study. The expected age-related reduction over time in student mathematics self-concept appeared to be mitigated in association with the longitudinal study. Nevertheless, the demonstration of a comparatively lower mathematics self-concept remained for girls overall and declined for Māori. Our results reinforce implications for future research into mathematics self-concept as a possible determinant of female student career choices. (shrink)

This paper describes a case study of a program called WATCH: Workshop for Actively Thinking Computationally and Historically. The focus of the program and this paper was on using mobile application development to promote historical thinking using a plantation site visit as the focus of inquiry. WATCH was delivered during an academic enrichment youth program at a major research university in the Southeast and served a total of 30 African American and Latino high school students from low socio-economic backgrounds. Through (...) the theoretical framework of historical thinking, this case study provides descriptions of the class sessions, students’ perceptions of and interests in history and students level of historical thinking through their apps. We make suggestions about how the instructional activities could be adapted for classrooms, discuss the tensions of using technology and inquiry pedagogy to support and promote historical learning, and review the program's impact on students’ agency as learners and critical consumers and producers of historical accounts. (shrink)

We give anecdotal accounts from our own experience of scientific theories which have been generally accepted as the ruling opinion long after sufficient evidence has been collected for their disproof. This has led us to the opinion that the normal scientific process, of working hypothesis followed by experimental test aimed at disproof, is being replaced by the ruling opinion followed by experiment aimed at confirmation. The apparently widespread adoption of this procedure may be postulated to arise in part from the (...) need for workers entering a new field of study to obtain grants and to get their results published. (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

To what extent does perceptual language reflect universals of experience and cognition, and to what extent is it shaped by particular cultural preoccupations? This paper investigates the universality~relativity of perceptual language by examining the use of basic perception terms in spontaneous conversation across 13 diverse languages and cultures. We analyze the frequency of perception words to test two universalist hypotheses: that sight is always a dominant sense, and that the relative ranking of the senses will be the same across different (...) cultures. We find that references to sight outstrip references to the other senses, suggesting a pan-human preoccupation with visual phenomena. However, the relative frequency of the other senses was found to vary cross-linguistically. Cultural relativity was conspicuous as exemplified by the high ranking of smell in Semai, an Aslian language. Together these results suggest a place for both universal constraints and cultural shaping of the language of perception. (shrink)

We propose Rhythmic Relating for autism: a system of supports for friends, therapists, parents, and educators; a system which aims to augment bidirectional communication and complement existing therapeutic approaches. We begin by summarizing the developmental significance of social timing and the social-motor-synchrony challenges observed in early autism. Meta-analyses conclude the early primacy of such challenges, yet cite the lack of focused therapies. We identify core relational parameters in support of social-motor-synchrony and systematize these using the communicative musicality constructs: pulse; quality; (...) and narrative. Rhythmic Relating aims to augment the clarity, contiguity, and pulse-beat of spontaneous behavior by recruiting rhythmic supports and relatable vitality; facilitating the predictive flow and just-ahead-in-time planning needed for good-enough social timing. From here, we describe possibilities for playful therapeutic interaction, small-step co-regulation, and layered sensorimotor integration. Lastly, we include several clinical case examples demonstrating the use of Rhythmic Relating within four different therapeutic approaches. These clinical case examples are introduced here and several more are included in the Supplementary Material. A suite of pilot intervention studies is proposed to assess the efficacy of combining Rhythmic Relating with different therapeutic approaches in playful work with individuals with autism. Further experimental hypotheses are outlined, designed to clarify the significance of certain key features of the Rhythmic Relating approach. (shrink)

The work of Robert Hooke on acoustics and music theory is a larger subject than might seem the case from studies of his career so far available. First, there are his experiments for the Royal Society which can be defined as purely acoustical, which anticipate later experiments performed by men such as J. Sauveur and E. Chladni. Second, there are passages in many of his writings which by extensive use of musical analogy attempt to account for all physical phenomena of (...) the universe, which operates on the principles of ‘harmony’ and ‘dissonance’. It is in this context that the hitherto unpublished manuscript presented at the end of this paper should be considered. This essay, which combines both the older tradition of the ‘praise of music’ and the newer consideration of the physical nature of musical sound, illustrates a particular aspect of Hooke's thought which exercised a profound influence on all his studies. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Available from UMI in association with The British Library. Requires signed TDF. ;The main part of the thesis concerns how things, in the sense of individuals, might have been. The topic is what limits there are on the counterfactual possibilities for individuals: in other words, what essential properties, if any, they have. ;In Chapters 3-6 three answers to this question that have been given in recent philosophical literature are examined. They are: that each thing has a unique individual essence ; (...) that there are features of the origin of an individual without which it could not possibly have existed ; and, finally, that there are sortal concepts that represent essential properties of the things that fall under them . ;All of these answers, and many of the arguments that have been given for them, are criticised. Sometimes the criticism takes the form of pointing to unpalatable consequences that result from the acceptance of the doctrine in question. Sometimes the criticism consists in pointing to difficulties or inadequacies in the arguments that have been presented in its favour. ;A preliminary chapter prepares the ground by setting out the conceptual framework, and the chief formal characteristics, of the essentialism discussed in the later chapters. Chapter 2 discusses the nature of necessary a posteriori truth, touching on questions in the philosophy of language and mind concerning the notion of de re thought. ;It is argued that essentialism about natural kinds raises problems of its own: some of these are discussed in Chapters 7 and 8. Here the main topic is the connection between semantic theory and natural kind essentialism. Concluding that the essentialism should be regarded as in an important sense independent of semantic theory, the chapters add to, and also criticise, the work of other writers who have reached the same verdict. Scepticism is also expressed about the independent plausibility of natural kind essentialism. ;Recent interest in essentialism owes its genesis chiefly to the work of Saul Kripke and Hilary Putnam: these figures stand in the background throughout the discussion. Among the other writers whose work is discussed are Baruch Brody, Gareth Evans, Graeme Forbes, Colin McGinn, J. L. Mackie, D. H. Mellor, Nathan Salmon, and David Wiggins. (shrink)

Historians Against History was first published in 1967. Minnesota Archive Editions uses digital technology to make long-unavailable books once again accessible, and are published unaltered from the original University of Minnesota Press editions. Professor Noble examines the basic philosophy and writing of six American historians, George Bancroft, Frederick Jackson, Charles A. Beard, Carl Becker, Vernon Louis Parrington, and Daniel J. Boorstin, and finds in them a common tradition which he calls anti-historical. He argues that this viewpoint is founded in (...) the frontier interpretation of American history, that American historians have served as the chief political theorists and theologians of this country since 1830, and that their writings can be interpreted as Jeremiads designed to preserve a national covenant with nature. (shrink)

In the course of history, many individuals have the dubious honor of being remembered primarily for an eponym of which they would disapprove. How many are aware that Joseph-Ignace Guillotin actually opposed the death penalty? Another notable case is that of Maria Agnesi, an Italian woman of privileged, but not noble, birth who excelled at mathematics and philosophy during the eighteenth century. In her treatise of 1748, Instituzioni Analitiche, she provided a comprehensive summary of the current state of knowledge (...) concerning both integral calculus and differential equations. Later in life she was elected to the Bologna Academy of Sciences and, in 1762, was consulted by the University of Turin for an opinion on the work of an up-and-coming mathematician named Joseph-Louis Lagrange. (shrink)