Light adaptation is modulated almost exclusively by changes in intracellular Ca2+ concentration, and other Ca2+-independent mechanisms are likely to play only a minor role. Changes in Ca2+i may be not only necessary for light adaptation to take place but sufficient to cause it.

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

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)

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together (...) researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals. (shrink)

The COVID-19 pandemic and global climate change crisis remind us that widespread trust in the products of the scientific enterprise is vital to the health and safety of the global community. Insofar as appropriate responses to these crises require us to trust that enterprise, cultivating a healthier trust relationship between science and the public may be considered as a collective public good. While it might appear that scientists can contribute to this good by taking more initiative to communicate their work (...) to public audiences, we raise a concern about unintended consequences of an individualistic approach to such communication. (shrink)

Despite decades of concerted efforts to communicate to the public on important scientific issues pertaining to the environment and public health, gaps between public acceptance and the scientific consensus on these issues remain stubborn. One strategy for dealing with this shortcoming has been to focus on the existence of scientific consensus on the relevant matters. Recent science communication research has added support to this general idea, though the interpretation of these studies and their generalizability remains a matter of contention. In (...) this paper, we describe results of a qualitative interview study on different models of scientific consensus and the relationship between such models and trust of science, finding that familiarity with scientific consensus is rarer than might be expected. These results suggest that consensus messaging strategies may not be effective. (shrink)

This volume collects essays by leading criminal law theorists to explore the principal themes in his work.

Scientists know that human activities, primarily fossil fuel combustion, are causing Earth’s temperature to increase. Yet in 2021, only 60% of the US population understood that human activities are the primary cause of global warming. We experimentally test whether information about the human causes of global warming influences Americans’ beliefs and concerns about global warming and support for climate policies. We find that communicating information about the human-causes of global warming increases public understanding that global warming is human-caused. This information, (...) both alone and with additional information about climate impacts and policy solutions, also increases public concern about global warming and support for climate policies, although the effects on climate concern and policy support are smaller. Importantly, the treatment effects are consistent across political party, with no backlash effects among Republicans. This suggests that when informed about climate change causes, impacts and solutions, most Americans can update their own climate change beliefs, risk perceptions, and policy support. (shrink)

The work of three present-day Sankritist-philosophers, _God and the World's Arrangement_ allows readers to engage directly with writings of the classical Indian philosophers Śaṅkara and Vācaspati, as well as some of their most acute critics, on the question of whether the existence of a creator God can be known by reason alone. Carefully selected and annotated with the needs of students foremost in mind, these new translations will be of interest to anyone wishing to see up close a newly set (...) gem of our philosophical inheritance from global antiquity. (shrink)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. (...) The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

It may seem faintly absurd to claim or imply that a Vergilian cento has suffered unjustified neglect from scholars. These works—of which there are sixteen, covering a period of over three centuries within Late Antiquity—are usually treated at best with amused tolerance, and at worst with angry disdain. Though always ingenious, sometimes funny, and occasionally informative about the reception of Vergil, they are seldom admired. Even among Italian scholars, some of whom have paid much attention to centos, a recession has (...) set in since the annus mirabilis of 1981, which saw two editions of the Medea of Hosidius Geta. Proba has, deservedly, attracted more attention than most; her aims and methods as a Christian poetess were carefully and illuminatingly studied twenty years ago by Reinhard Herzog, and her interest as a female Roman aristocrat has brought her further attention, especially in recent years. The main aim of the present article is to suggest a particular context and a serious purpose for her cento. A postscript will show that it went on to enjoy considerable popularity until the end of the century, and an introductory section will discuss its date, but very briefly, since Matthews has convincingly said most of what needs to be said about a recent attempt to redate it. Proba's preface, much of it not in cento form, calls for detailed treatment from various angles—textual, literary, historical—and will be explored in a separate article. (shrink)

It may seem faintly absurd to claim or imply that a Vergilian cento has suffered unjustified neglect from scholars. These works—of which there are sixteen, covering a period of over three centuries within Late Antiquity—are usually treated at best with amused tolerance, and at worst with angry disdain. Though always ingenious, sometimes funny, and occasionally informative about the reception of Vergil, they are seldom admired. Even among Italian scholars, some of whom have paid much attention to centos, a recession has (...) set in since the annus mirabilis of 1981, which saw two editions of the Medea of Hosidius Geta. Proba has, deservedly, attracted more attention than most; her aims and methods as a Christian poetess were carefully and illuminatingly studied twenty years ago by Reinhard Herzog, and her interest as a female Roman aristocrat has brought her further attention, especially in recent years. The main aim of the present article is to suggest a particular context and a serious purpose for her cento. A postscript will show that it went on to enjoy considerable popularity until the end of the century, and an introductory section will discuss its date, but very briefly, since Matthews has convincingly said most of what needs to be said about a recent attempt to redate it. Proba's preface, much of it not in cento form, calls for detailed treatment from various angles—textual, literary, historical—and will be explored in a separate article. (shrink)

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released (...) DR9 and DR10 samples. Assuming a concordance Λ cold dark matter cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = at z = 0.32 and DV = at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = and H =. Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Cost-benefit analysis is a widely used governmental evaluation tool, though academics remain skeptical. This volume gathers prominent contributors from law, economics, and philosophy for discussion of cost-benefit analysis, specifically its moral foundations, applications and limitations. This new scholarly debate includes not only economists, but also contributors from philosophy, cognitive psychology, legal studies, and public policy who can further illuminate the justification and moral implications of this method and specify alternative measures. These articles originally appeared in the Journal of Legal Studies. (...) Contributors: - Matthew D. Adler - Gary S. Becker - John Broome - Robert H. Frank - Robert W. Hahn - Lewis A. Kornhauser - Martha C. Nussbaum - Eric A. Posner - Richard A. Posner - Henry S. Richardson - Amartya Sen - Cass R. Sunstein - W. Kip Viscusi. (shrink)

Introduction, by R. A. Markus.--St. Augustine and Christian Platonism, by A. H. Armstrong.--Action and contemplation, by F. R. J. O'Connell.--St. Augustine on signs, by R. A. Markus.--The theory of signs in St. Augustine's De doctrina Christiana, by B. D. Jackson.--Si fallor, sum, by G. B. Matthews.--Augustine on speaking from memory, by G. B. Matthews.--The inner man, by G. B. Matthews.--On Augustine's concept of a person, by A. C. Lloyd.--Augustine on foreknowledge and free will, by W. L. Rowe.--Augustine (...) on free will and predestination, by J. M. Rist.--Time and contingency in St. Augustine, by R. Jordan.--Empiricism and Augustine's problems about time, by H. M. Lacey.--Political society, by P. R. L. Brown.--The development of Augustine's ideas on society before the Donatist controversy, by F. E. Cranz.--De Civitate Dei, XV, 2, and Augustine's idea of the Christian society, by F. E. Cranz.--Chronological table.--Note on further reading (p. [422]-423). (shrink)

The relation between method, concept and theory in science is complicated. I seek to shed light on that relation by considering an instance of it in systematics: The additional challenges phylogeneticists face when reconstructing phylogeny not at a single level, but simultaneously at multiple levels of the hierarchy. How does this complicate the task of phylogenetic inference, and how might it inform and shape the conceptual foundations of phylogenetics? This offers a lens through which the interplay of method, theory and (...) concepts may be understood in systematics, which, in turn, provides data for a more general account. (shrink)

Against the background of a recent exchange between Cristina Lafont and Hubert Dreyfus, I argue that Heidegger's method of ?formal indication? is at the heart of his attempt in Sein und Zeit to answer ?the ontological question of the being of the ?sum?? (SZ, p. 46). This method works reflexively, by picking out certain essential features of one's first-person singular being at the outset of its investigation that are implicit in the question ?what is it to be the entity I (...) am?? On the basis of these features, various further a priori, ontological structures (care and temporality) that constitute one as a first-person singular entity then become accessible. Formal indication is thus formal in two senses: it officially designates or signals certain first-person singular phenomena as the topic of investigation, and it picks out features which define the ontological form of the entity in question. It is thereby the method by which a legitimately transcendental account of our being may be begun to be generated by each of us from out of our factical, immanent existence. (shrink)

Heidegger’s early project aims to articulate the form of our being as Dasein, and he says that for this usually hidden form to become accessible, a certain kind of “mood” is required of the philosopher. This “ground-mood” he identifies in Sein und Zeit as anxiety. He also, however, presents anxiety as a mood anyone, philosopher or not, experiences when there is some significant breakdown in the living of her life. I argue here that there are largely unrecognized problems with this (...) conflation of methodological and “existential” moods, but that there is nevertheless a compelling methodological account of anxiety that can be teased apart from the existentialist one: methodologically understood, anxiety is a self-affected state of the ontologist, one that results from her asking ontological questions of herself, and, by imagining crisis or breakdown, withdrawing from her determinate situation to a position where she can see the form of her own activity as questioner and imaginer. I draw out some consequences this has for how we should understand the place of ontological understanding in living one’s life, and I conclude by briefly showing how my reading helps us see Heidegger as developing key elements in the work of Descartes and Kant. (shrink)

Abstract: Heidegger's Sein und Zeit (SZ) is commonly viewed as one of the 20th century's great anti-Cartesian works, usually because of its attack on the epistemology-driven dualism and mentalism of modern philosophy of mind or its apparent effort to ‘de-center the subject’ in order to privilege being or sociality over the individual. Most who stress one or other of these anti-Cartesian aspects of SZ, however, pay little attention to Heidegger's own direct engagement with Descartes, apart from the compressed discussion in (...) SZ§§19–21. I here show through a careful reading of Heidegger's lectures on Descartes from the years immediately preceding SZ that, while he has sharp criticisms of Descartes and certain ‘Cartesian’ aspects of modern philosophy along the lines commonly recognized, he also aims to disclose what he calls the ‘positive possibilities’ in Descartes and the philosophy he inspired. I detail a number of these and then show that they force us to see Heidegger's own early project as largely unconcerned with dualism and mentalism per se, and much more with questions of the philosophical methodology that gives rise to them. Moreover, I show that a careful reading of Heidegger's treatment of the cogito makes clear that he is no serious way attempting to ‘de-center the subject’ and that the fundamental question of the ‘analytic of Dasein’ is one that takes Descartes as an immediate jumping off point: how can I articulate what I understand myself to be as the general kind of entity I am, and on what besides me does my being depend? (shrink)

Cristina Lafont's recent reading of Heidegger offers a powerful formulation of the widespread view that once one recognizes our `facticity' and the role of language in shaping it, there is no room left to talk about transcendental structures of meaning or experience. In this article I challenge this view. I argue that Lafont inaccurately conflates what Heidegger calls our `understanding of being' with that which language discloses. In order to show that the philosophical motivation for this conflation is unsound, I (...) also argue that Lafont's own positive theory of meaning itself tacitly assumes a distinction between factical and transcendental, and so rests on exactly what she finds problematic in Heidegger. This still leaves a puzzle as to how factical individuals are actually able to grasp anything transcendental, so I conclude by sketching Heidegger's method of `formal indication', which is meant to show precisely how this can be done. (shrink)

I begin with a brief exposition of what is positive in Haugeland's interpretation of Heidegger. At the same time, I show how Haugeland subtly shifts the ground so as to make it possible to read into the texts his own idea that being is the entity-beholden, variable, normative basis for ways of life. I then argue that what Heidegger himself says about the being of available (zuhanden) entities, i.e., things of use or equipment (Zeug), doesn’t fit with Haugeland’s normativity-oriented account. (...) I develop this argument further through a look at Heidegger’s treatment of occurrent (vorhanden) nature as he elaborates that in his reading of Kant. This allows us to see how Heidegger follows Kant in thinking of the forms of being as spontaneous but non-arbitrary creations we produce for ourselves via what Kant called imagination, which activity Heidegger takes to be the self-temporalizing of Dasein identified but only opaquely described in SZ. From there, I show how we might generalize from Heidegger’s Kant’s treatment of the occurrent to a broader account in which other regional understandings of being, including that of the available, may also be understood as emerging from our temporalizing/imaginative activity. This shows what Heidegger’s overall project of fundamental ontology looks like, and how it could be completed in a way he himself didn't, if an understanding of being is an understanding of forms not norms. (shrink)