The recent surge of discoveries concerning the structural organization of nucleosomes, together with genetic evidence of highly specialized roles for the histones in gene regulation, have brought a renewed need for a detailed understanding of nucleosomal anatomy. Here we review recent structural advances leading to a new level of understanding of the nucleosome and chromatin fibre structure. We discuss the problems and challenges for existing models of chromatin structure and, in particular, consider how linker histones may bind within the nucleosome, (...) together with the implications of their association for the structure of the chromatin fibre. (shrink)

Nucleosome positioning is proposed to have an essential role in facilitating the regulated transcription of eukaryotic genes. Some transcription factors can bind to DNA when it is appropriately wrapped around the histone core, others cannot bind due to the severe deformation of DNA structure. The staged assembly of nucleosomes and positioning of histone‐DNA contacts away from promoter elements can facilitate the access of transcription factors to DNA. Positioned nucleosomes can also facilitate transcription through providing the appropriate scaffolding to bring regulatory (...) factors bound at dispersed sites into juxtaposition. (shrink)

Nucleosome positioning is proposed to have an essential role in facilitating the regulated transcription of eukaryotic genes. Some transcription factors can bind to DNA when it is appropriately wrapped around the histone core, others cannot bind due to the severe deformation of DNA structure. The staged assembly of nucleosomes and positioning of histone‐DNA contacts away from promoter elements can facilitate the access of transcription factors to DNA. Positioned nucleosomes can also facilitate transcription through providing the appropriate scaffolding to bring regulatory (...) factors bound at dispersed sites into juxtaposition. (shrink)

Recent research investigating the language–thought interface in the spatial domain points to representations of the horizontal and vertical dimensions that closely resemble those posited by Jeffery et al. However, the findings suggest that such representations, rather than being tied to navigation, may instead reflect more general properties of the perception of space.

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

The Representational Theory of Measurement (RTM), especially the canonical three volume Foundations of Measurement by Krantz et al., is a landmark accomplishment in our understanding of measurement. Despite this, it has been far from easy to pinpoint what exactly we can learn about measurement from RTM, and who the target audience for RTM’s formal results should be. In what sense does RTM provide foundations of measurement, and what is the philosophical significance of such foundations? I argue that RTM provides semantic (...) foundations of measurement, and that their philosophical significance lies in a shift towards structural representation. (shrink)

What are physical quantities, and in particular, what makes them quantitative? This book presents an original answer to this question through the novel position of substantival structuralism, arguing that quantitativeness is an irreducible feature of attributes, and quantitative attributes are best understood as substantival structured spaces.

Research into expertise is relatively common in cognitive science concerning expertise existing across many domains. However, much less research has examined how experts within the same domain assess the performance of their peer experts. We report the results of a modified think-aloud study conducted with 18 pilots . Pairs of same-ranked pilots were asked to rate the performance of a captain flying in a critical pre-recorded simulator scenario. Findings reveal considerable variance within performance categories, differences in the process used as (...) evidence in support of a performance rating, different numbers and types of facts identified, and differences in how specific performance events affect choice of performance category and gravity of performance assessment. Such variance is consistent with low inter-rater reliability. Because raters exhibited good, albeit imprecise, reasons and facts, a fuzzy mathematical model of performance rating was developed. The model provides good agreement with observed variations. (shrink)

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as (...) economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. -/- To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. -/- We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations. (shrink)

All parties involved in researching, developing, manufacturing, and distributing COVID-19 vaccines need guidance on their ethical obligations. We focus on pharmaceutical companies' obligations because their capacities to research, develop, manufacture, and distribute vaccines make them uniquely placed for stemming the pandemic. We argue that an ethical approach to COVID-19 vaccine production and distribution should satisfy four uncontroversial principles: optimising vaccine production, including development, testing, and manufacturing; fair distribution; sustainability; and accountability. All parties' obligations should be coordinated and mutually consistent. For (...) instance, companies should not be obligated to provide host countries with additional booster shots at the expense of fulfilling bilateral contracts with countries in which there are surges. Finally, any satisfactory approach should include mechanisms for assurance that all parties are honouring their obligations. This assurance enables countries, pharmaceutical companies, global organisations, and others to verify compliance with the chosen approach and protect ethically compliant stakeholders from being unfairly exploited by unethical behaviour of others. (shrink)

Recent literature on causation invokes a distinction between deviant and default behavior to account for token causation. Critical examination of two prominent attempts to employ a distinction between deviants and defaults reveals that the distinction is far from clear. I clarify and develop the distinction by appeal to the notion of a modally robust process, and show how the distinction can be employed by causal process theorists to respond to cases of causation by omission. This shows that the default/deviant distinction (...) is not so much a tool for counterfactual accounts of causation, but rather for causal process theory. (shrink)

Mitochondrial function is achieved through the cooperative interaction of two genomes: one nuclear (nuDNA) and the other mitochondrial (mtDNA). The unusual transmission of mtDNA, predominantly maternal without recombination is predicted to affect the fitness of male offspring. Recent research suggests the strong sexual dimorphism in aging is one such fitness consequence. The uniparental inheritance of mtDNA results in a selection asymmetry; mutations that affect only males will not respond to natural selection, imposing a male‐specific mitochondrial mutation load. Prior work has (...) implicated this male‐specific mutation load in disease and infertility, but new data from fruit flies suggests a prominent role for mtDNA in aging; across many taxa males almost invariably live shorter lives than females. Here we discuss this new work and identify some areas of future research that might now be encouraged to explore what may be the underpinning cause of the strong sexual dimorphism in aging.Editor's suggested further reading in BioEssays: Mitonuclear match: Optimizing fitness and fertility over generations drives ageing within generations AbstractMitochondrial manoeuvres: Latest insights and hypotheses on mitochondrial partitioning during mitosis in Saccharomyces cerevisiae AbstractMitochondria and the culture of the Borg Abstract. (shrink)

This paper describes a novel perspective on the foundations of mathematics: how mathematics may be seen to be largely about “information compression via the matching and unification of patterns”. That is itself a novel approach to IC, couched in terms of nonmathematical primitives, as is necessary in any investigation of the foundations of mathematics. This new perspective on the foundations of mathematics reflects the facts that mathematics is almost exclusively the product of human brains, and has been developed, as an (...) aid to human thinking, mathematics is likely to be consonant with much evidence for the importance of IC in human learning, perception, and cognition. This perspective on the foundations of mathematics has grown out of a long-term programme of research developing the SP Theory of Intelligence and its realization in the SP Computer Model, a system in which a generalised version of ICMUP—the powerful concept of SP-multiple-alignment—plays a central role. This paper shows with an example how mathematics, without any special provision, may achieve compression of information. Then, it describes examples showing how variants of ICMUP may be seen in widely used structures and operations in mathematics. Examples are also given to show how several aspects of the mathematics-related disciplines of logic and computing may be understood as ICMUP. Also discussed is the intimate relation between IC and concepts of probability, with arguments that there are advantages in approaching AI, cognitive science, and concepts of probability via ICMUP. Also discussed is how the close relation between IC and concepts of probability relates to the established view that some parts of mathematics are intrinsically probabilistic, and how that latter view may be reconciled with the all-or-nothing, “exact,” forms of calculation or inference that are familiar in mathematics and logic. There are many potential benefits and applications of the mathematics-as-IC perspective. (shrink)

Measurement realism, the view that measurement targets quantitative attributes and that not all attributes are quantitative, has come under attack both from metrologists and philosophers. In this paper, I take a close look at two influential arguments against measurement realism: the argument from obsolescence and the argument from coordination. I concede that these arguments do challenge the epistemological position traditionally taken by measurement realists, but argue that the metaphysical core of measurement realism survives the challenge posed by these arguments. This (...) metaphysical core is vital to maintaining a clear and ambitious standard for successful measurement. (shrink)

The Simplicity and Power (SP) theory (Wolff 2003a) provides support for Pothos's proposals by illustrating how the effect of “rules” and “similarity” may be achieved within an integrated model that makes no explicit provision for either concept. The theory is described here in outline with simple examples to show how rules and similarity can emerge as properties of the system in learning, reasoning, categorization, and the parsing of language.

Interest in a hydrogen economy has grown significantly in the past decade. However, the success of old technologies that are being re-engineered to work on hydrogen, as well as the creation of new hydrogenbased technologies, hinges upon public interest in and demand for such technologies. With increasing investments in the research and development of hydrogen technologies, there exists a need to monitor public attitudes toward hydrogen to ensure its success as an alternative energy carrier. To address this need, two surveys (...) were conducted. The results of the first survey give insights about how colored information influences the public acceptance of hydrogen, and the results of the second survey elucidate what trade-offs the public is willing to accept during the transition to a hydrogen economy. Furthermore, the research highlights how hydrogen knowledge and acceptance differ among age, education, and gender groups. (shrink)

Cambridge’deki büyük akademik cemaatin sakinleri olan bizler bir araya geldik ve hoşgörü ve onun egemen politik iklim içerisindeki yeri hakkında dostça ama ateşli bir tartışma yürüttük. Okuyucu, bizim nerelerde aynı düşüncede olmadığımızı bulmakta hiçbir zorluk çekmeyecektir. Diğer taraftan, farklı başlangıç noktalarından ve farklı yollardan hareketle yaklaşık olarak aynı yere ulaştık. Her birimiz için, egemen hoşgörü kuramı ve pratiğinin, incelendiği takdirde, korkunç politik gerçekleri gizlemeye yarayan bir maske olduğu ortaya çıktı. Kızgınlığın tonu makaleden makaleye keskin bir şekilde artmakta; belki de boş (...) yere, okuyucuların bu noktaya getiren akıl yürütmeyi takip edeceklerini umuyoruz. Nihayetinde bu kızgınlık hem kafa hem de kalpte ikamet etmektedir…. (shrink)

Social inequalities in health in the UK persist despite attempts to reduce them. We argue that work and pensions constitutes an area of intervention where there is potential to make change happen. We propose that workers who are exposed to significant health risks through their occupation should be allowed to draw their state pension earlier, based on a minimum number of years in the workforce. We model this proposal on similar policies in other European countries. In our modification, the pension (...) age and the retirement age would be separated, such that workers can receive a state pension whether or not they choose to continue working. This arrangement may encourage workers either to reduce their working hours or to change to less demanding or harmful work. The health of these workers would thereby benefit from reduced exposure to a harmful work environment, reduced stress and more opportunities for rest and relaxation. However, it has also been suggested that retirement is bad for mental health. In response, our proposal enables workers to phase in full retirement over a period of part-time work, and we believe that this would counter any potential negative effects on health caused by retirement. (shrink)

Toward the end of his life, the Russian psychologist L.S. Vygotsky turned away from his earlier work that he has become famous for only to sow the seeds for a new theory. In this theory, affect was to play a central role, there was to be a primacy of social relations, and anything mental (mind, thought, self, other, knowledge) was an event rather than a thing. This is essentially a transactional perspective. In this book, the author articulates a transactional psychology (...) of education drawing on the works of G.H. Mead, J. Dewey, G. Bateson, F. Mikhailov, and E. Il'enkov. All theoretical positions are developed out of videotaped exchanges, thereby giving concrete character to every psychological concept articulated. (shrink)

The question 'Why should I obey the law?' introduces a contemporary puzzle that is as old as philosophy itself. The puzzle is especially troublesome if we think of cases in which breaking the law is not otherwise wrongful, and in which the chances of getting caught are negligible. Philosophers from Socrates to H.L.A. Hart have struggled to give reasoned support to the idea that we do have a general moral duty to obey the law but, more recently, the greater number (...) of learned voices has expressed doubt that there is any such duty, at least as traditionally conceived. (shrink)

Introduction: What is the critical spirit?--Utopianism, ancient and modern, by M.I. Finley.--Primitive society in its many dimensions, by S. Diamond.--Manicheanism in the Enlightenment, by R.H. Popkin.--Schopenhauer today, by M. Horkheimer.--Beginning in Hegel and today, by K.H. Wolff.--The social history of ideas: Ernst Cassirer and after, by P. Gay.--Policies of violence, from Montesquieu to the Terrorist, by E.V. Walter.--Thirty-nine articles: toward a theory of social theory, by J.R. Seeley.--History as private enterprise, by H. Zinn.--From Socrates to Plato, by H. Meyerhoff.--Rational (...) society and irrational art, by H. Read.--The quest for the Grail; Wagner and Morris, by C.E. Schorske.--Valéry; Monsieur Teste, by L. Goldmann.--History and existentialism in Sartre, by L. Krieger.--German popular biographies; culture's bargain counter, by L. Lowenthal.--The Rechtsstaat as magic wall, by O. Kirchheimer. (shrink)

Bibliographical footnotes. Introduction: What is the critical spirit?--Utopianism, ancient and modern, by M.I. Finley.--Primitive society in its many dimensions, by S. Diamond.--Manicheanism in the Enlightenment, by R.H. Popkin.--Schopenhauer today, by M. Horkheimer.--Beginning in Hegel and today, by K.H. Wolff.--The social history of ideas: Ernst Cassirer and after, by P. Gay.--Policies of violence, from Montesquieu to the Terrorist, by E.V. Walter.--Thirty-nine articles: toward a theory of social theory, by J.R. Seeley.--History as private enterprise, by H. Zinn.--From Socrates to Plato, by (...) H. Meyerhoff.--Rational society and irrational art, by H. Read.--The quest for the Grail; Wagner and Morris, by C.E. Schorske.--ValeÌ ry; Monsieur Teste, by L. Goldmann.--History and existentialism in Sartre, by L. Krieger.--German popular biographies; culture's bargain counter, by L. Lowenthal.--The Rechtsstaat as magic wall, by O. Kirchheimer. Revolution from above: some notes on the decision to collectivize Soviet agriculture, by E.H. Carr.--Winston Churchill, power politician and counter revolutionary, by A.J. Mayer.--Brahmins and business, 1870-1914; a hypothesis on the social basis of success in American history, by G. Kolko.--On the limits of professional thought, by M.R. Stein.--The limits of integration, by P. Mattick.--The society nobody wants; a look beyond Marxism and liberalism.--Marcuse as teacher, by W. Leiss, J.D. Ober and E. Sherover.--Marcuse bibliography, by W. Leiss, J.D. Ober and E. Sherover (p. 427-433). (shrink)